This study investigates potentially toxic elements (PTEs) concentrations in both washed and unwas... more This study investigates potentially toxic elements (PTEs) concentrations in both washed and unwashed leaves of Calotropis procera and in the soil near its roots along roadsides with varying vehicular traffic densities. Additionally, it explores the plant's physiological, biochemical, and morpho-anatomical responses to PTEs exposure. Samples of unwashed and washed leaves from roadside areas with very high, high, medium, and low traffic densities, as well as control sites located 100-500 meters away from roads, were analyzed for PTEs concentrations, physicochemical properties and morpho-anatomical characteristics. A paired sample t-test revealed significant differences (p<0.05) in PTEs concentrations, except for Mn, with higher levels in unwashed leaves compared to washed ones. The highest PTEs concentrations were observed in areas with very high traffic density (VHD), followed by high-density (HD), moderate (MD), and low-density (LD) areas. The study also explored the role of soil as a sink for these contaminants, revealing a strong positive correlation between vehicular density and PTEs level in soil. The bioaccumulation factor (BCF) indicated significant uptake of Pb, Cd, Cr, Mn, and Cu, with lower values for other elements. The study also assessed physiological and biochemical parameters, including chlorophyll content, ascorbic acid, antioxidant potential, and membrane stability index, all of which showed significant variations across sites with different traffic densities. Morphological and anatomical variations, such as reductions in leaf area, leaf thickness, and stomatal dimensions, were observed in polluted areas. Principal Component Analysis (PCA) highlighted the correlations between PTEs, morphological traits, and vehicular density, with notable negative effects at high traffic sites. In conclusion, C. procera is an effective phyto-accumulator and bioindicator of PTEs pollution, with high ecological adaptability, making it suitable for phytoremediation and pollution monitoring. This study highlights the impact of vehicular pollution on plant health and stresses the importance of monitoring these factors for environmental management.
Sulfated flavonoids, also named flavonoid sulfates, are a class of polyphenol derivatives from va... more Sulfated flavonoids, also named flavonoid sulfates, are a class of polyphenol derivatives from various plants often with a long history of use in traditional medicine around the world, that play an important role in secondary metabolism, chemical defense, and growth regulation of plants, and with significant and potential health benefits. Sulfated flavonoids are produced by a substitution reaction of a flavonoid moiety and a sulfate donor, where transfer of a sulfate group to hydroxyl groups in the flavonoid structure is catalyzed, either naturally or synthetically, by the enzyme sulfotransferase. Of note, several monocotyledonous and dicotyledonous plant families have been reported for their content of sulfated flavonoids. Various medically important bioactivities have been reported for sulfated flavonoids, including antitumor, antidiabetic, antimicrobial, and antiviral properties, and which we discuss in this review. The present review focuses on sulfated flavonoids extracted from plants but also discuss some chemically synthesized sulfated flavonoids explored, e.g., for their (potential) anticoagulant properties. This review aims to summarize the published data on naturally occurring and synthetic sulfated flavonoids, paying particular attention to their structural variations and occurrence, biosynthesis aspects, methods of identification, extraction and isolation, and biological activities. The review covers literature published in English, spanning the entire period from the first report in 1971 to January 2025. Finally, the current work emphasizes this class of compounds as a source of potential candidates for the development of new pharmaceutical drugs with beneficial bioactivities.
Synthesis and characterization of thymol-derived phenoxy acetamide derivatives using DFT, molecular docking, and parasitological investigations
Frontiers in Chemistry, 2025
Novel phenoxy acetamide derivatives based on a thymol moiety were synthesized for target parasito... more Novel phenoxy acetamide derivatives based on a thymol moiety were synthesized for target parasitological investigation. The newly synthesized compounds, 5a, 5b, 7a, 7b, and 9, were synthesized as phenoxy acetamide derivatives containing a phthalimide or naphthalimide ring through a condensation reaction with various acid anhydrides. Their structures were confirmed based on spectral data derived through Fourier-transform infrared, proton and carbon-13 nuclear magnetic resonance, and elemental analyses. The parasitological, biochemical, and immunological activities of the compounds were measured. The screened compounds were subjected to molecular docking in the active site of CpCDPK1, in addition to analyses based on Lipinski's rule and SwissADME. The results showed that compounds 5a, 5b, and 7b demonstrated promising antiparasitic activity, characterized by high gastrointestinal absorption and favorable drug-likeness profiles. Furthermore, 5a and 7b exhibited higher binding affinities than that of the reference drug. In practical assessments, compound 7b exhibited the highest percentage reduction in oocyst counts (67%). Density functional theory calculations were performed to assess the thermodynamic stability, molecular geometry, frontier molecular orbital energy gaps, and molecular electrostatic potentials of compounds 5a, 5b, 7a, 7b, and 9.Phenoxy acetamide derivatives based on a thymol moiety were synthesized through condensation reactions with a series of acid anhydrides. As shown in Scheme 1, 2-(2-isopropyl-5methylphenoxy)acetohydrazide (3) was reacted with different acid anhydrides, including phthalic anhydride (4a), 1,2,4-benzene tricarboxylic acid anhydride (4b), 1,8-naphthalic anhydride (6a), 4amino-1,8-naphthalic anhydride (6b), and pyromellitic dianhydride (8) in dimethylformamide (DMF) and glacial acetic acid under reflux conditions for 4-6 h to afford compounds 5a, 5b, 7a, 7b, and 9, respectively.The structures of the synthesized compounds 5a, 5b, 7a, 7b, and 9 were confirmed using spectroscopic data. The proton nuclear magnetic resonance ( 1 H-NMR) spectrum showed characteristic singlet peaks for NH (10.08-10.90 ppm) and aliphatic CH3 (1.13-2.27 ppm). The infrared (IR) spectra of all synthesized compounds showed two sharp bands of C=O (conjugated anhydride) at ν = 1792 cm -1 and 1744 cm -1 .
Naphthyl chalcone derivatives with a D-A-D architecture were designed and synthesized using Clais... more Naphthyl chalcone derivatives with a D-A-D architecture were designed and synthesized using Claisen-Schmidt condensation to explore their potential for optoelectronic applications, particularly in organic photovoltaics. Among the synthesized compounds, compounds 17 and 18 stood out due to their notable photophysical and electrochemical properties. The chalcones were characterized through photophysical and electrochemical analyses. Experimental results revealed significant absorption and emission in visible regions, with high Stokes shifts and favorable fluorescence quantum yields, especially for compounds 17 and 18. Cyclic voltammetry showed promising oxidation/reduction potentials, highlighting their charge transport capabilities. DFT and TD-DFT were used to investigate the electronic structure, molecular orbitals, optical properties, and electronic transitions. Computational analysis provided insights into frontier molecular orbitals, dipole moments, density of states, reactivity descriptors, charge transfer integrals and reorganization energy, molecular electrostatic potential, and transition density matrices. The findings demonstrate that these chalcones exhibit favorable optical properties and electrochemical characteristics, making them promising candidates for further experimental studies in OPV devices.
A novel platinum(IV) supramolecular complex; [PtCl 2 (2,2′-bipy) 2 ](PtCl 6) was synthesized in a... more A novel platinum(IV) supramolecular complex; [PtCl 2 (2,2′-bipy) 2 ](PtCl 6) was synthesized in aqueous acetonitrile solution at ambient temperature with constant stirring. The structure was confirmed by elemental analysis, FT-IR, UV-vis, NMR spectroscopy, and single-crystal X-ray diffraction, revealing a unique distorted octahedral geometry and a three-dimensional network stabilized by hydrogen bonding and π-π stacking. DNA binding studies, including electronic absorption titration and viscometry, indicated a groove binding mechanism with a binding constant (K b) of 5.00 × 10⁶ M-1. Molecular docking with DNA (PDB ID: 1BNA) and cancer-related proteins (PDB codes: 3ig7, 3eqm, 4fm9) supports these interactions, while in vitro anticancer assays demonstrated potent cytotoxicity with IC₅₀ values of 41.37 μM for HepG2, 47.62 μM for HCT116, and 73.90 μM for MDA-MB-231 cells, outperforming cisplatin in selectivity. This study not only advances our understanding of structure-activity relationships in platinum-based complexes but also highlights the potential of this complex as a promising candidate for developing more effective and less toxic anticancer agents.
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metaboli... more Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metabolic dysregulation, oxidative stress, amyloid-β (Aβ) aggregation, metal dyshomeostasis, and mitochondrial dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. This study investigates the metabolic effects of the alkaloids galantamine (GAL) and lycorine (LYC) in differentiated SH-SY5Y neuroblastoma cells, an established in vitro model for AD, which acquire a neuronal phenotype upon differentiation. Using untargeted and targeted NMR-based metabolomics combined with multivariate statistical analysis, we analyzed extracellular metabolic profiles under basal conditions and following Aβ42 exposure, both in the presence and absence of GAL and LYC. Our findings reveal distinct metabolic responses to Aβ toxicity, with significant alterations in pyruvate and glutamine metabolism. Both GAL and LYC contributed to the restoration of glutamine and lysine homeostasis, but LYC had a more pronounced effect, better sustaining cellular energy balance and mitochondrial function. Unlike LYC, GAL treatment was associated with pyruvate accumulation, highlighting a distinct metabolic response between the two compounds. These variations may reflect distinct mechanisms of action, potentially influencing their therapeutic roles in counteracting Aβ-induced toxicity. This study highlights the value of metabolic profiling for assessing neuroprotective agents and reinforces the potential of natural alkaloids in this context.
This study conducts a comprehensive metabolomic profiling of the Zygophyllum (Z) coccineum plant,... more This study conducts a comprehensive metabolomic profiling of the Zygophyllum (Z) coccineum plant, a halophyte prevalent in Saudi Arabia and Egypt, employing gas chromatography-mass spectrometry (GC–MS), liquid chromatography-mass spectrometry (LC–MS), and nuclear magnetic resonance (NMR) spectroscopy. Recognizing the plant’s significance in traditional medicine, we explore its adaptative mechanisms and potential pharmacological applications through the identification of metabolites. Various solvents, namely acetonitrile–water (AcW), isopropanol-methanol–water (IMW), and methanol–water (MW) were utilized for metabolite extraction. Our results reveal a diverse spectrum of metabolites, including amino acids, sugars, organic acids, alkaloids, steroids, and terpenoids, with significant variations in extraction efficiency and metabolite composition across solvents. Identified metabolites indicate the reason for using Z. coccineum leaves as traditional medicine in Saudi Arabia, and Egypt because of consist of several phytochemical metabolites used for the treatment of diabetes, kidney diseases, cancer, urinary tract secretions, dental pain, tumors, stomach pain, smallpox, asthma, rheumatism, gout, infections, hypertension, burns, and blood pressure, found in the extractions by the three different solvents on the analysis through GC/LC–MS spectrometry. Identified metabolites and their statistical analyses, including principal component analysis (PCA) and variable importance in projection (VIP), indicated that AcW in GC–MS provides a superior number of metabolites, clustering, and variability statistical analysis, while MW excels in LC–MS metabolic profiling and their statistical analysis compared to other solvents. These multilayers of solvents and analytical techniques approach underscores the importance of solvents in enhancing metabolomic studies, thereby facilitating a deeper understanding of the phytochemicals within Z. coccineum and their medicinal potential. Enhancing our knowledge of the plant’s metabolomics may inform future applications in pharmacology and agriculture.
Cancer presents a formidable and complex foe, standing as one of the foremost contributors to dis... more Cancer presents a formidable and complex foe, standing as one of the foremost contributors to disease-related fatalities across the globe. According to data from the Global Cancer Observatory (GLOBOCAN), projections indicate a staggering 28.4 million cases of cancer, encompassing both new diagnoses and deaths, by 2040. Therefore, developing effective and comprehensive treatment approaches for cancer patients is essential and the conventional approved treatments for cancers are associated with various harmful side effects. Our study aims to address the critical and widespread need for alternative therapies that can effectively combat cancer with minimal side effects.
The present contribution outlines a targeted approach using Lysine Specific Demethylase 1 (LSD1) to evaluate novel cyano-pyrimidine pendant chalcone derivatives as potential antiproliferative agents. Two sets of novel cyano-pyrimidine pendant chalcone derivatives were produced, and molecular docking was performed on the LSD1 protein. The ligands A1 and B1 belonging to series A and B, respectively, were found to have the highest docking scores of −11.095 and −10.773 kcal/mol, in that order. The ADME and toxicity studies of the ligands showed promising responses with respect to various pharmacokinetic and physicochemical parameters. The Molecular dynamics (MD) simulation results indicated effective diffusion of both complexes inside the protein cavity, facilitated by prominent interactions with various amino acids. Additionally, the complexes displayed high relative binding free energy. The computational screening of ligands indicates that ligands A1 and B1 exhibit potential for further exploration using various in vitro and in vivo techniques. These ligands may then serve as promising leads in the discovery of cancer drugs. The in-silico screening of the novel library of cyano-pyrimidine pendant chalcone derivatives was performed with a combination of molecular docking, MM-GBSA, ADME, toxicity and MD simulation. Molecular docking and MM-GBSA were conducted using the Glide and Prime tools, respectively, of the Schrödinger suite 12.8. The ligands were analysed for ADME using the Swiss ADME, while toxicity risks were evaluated using Osiris Property Explorer. Additionally, a 400ns MD simulation of LIGA1 and LIGB1 against the protein LSD1 was performed using the Desmond tool of Schrödinger suite 12.8 to validate the docking results and analyse the behaviour and stability of the complexes.
Background/Objectives: Although malaria is one of the oldest known human diseases, it continues t... more Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.
Repurposing eugenol and cinnamaldehyde as potent antimicrobial agents: A comprehensive in-vitro and in-silico study
Bioorganic Chemistry, 2025
Multi-drug-resistant (MDR) pathogens represent a critical global health threat, necessitating the... more Multi-drug-resistant (MDR) pathogens represent a critical global health threat, necessitating the development of novel antimicrobial agents with broad-spectrum activity and minimal toxicity. This study investigates the antimicrobial and anti-biofilm properties of 4-Allyl-2-methoxyphenol (eugenol, EU) and (E)-3-Phenylprop-2-enal (cinnamaldehyde, CN) against 19 clinically significant pathogens through a combination of in-vitro assays and in-silico analyses. EU displayed remarkable activity, particularly against Aspergillus niger (20.5 ± 0.5 mm), and strong binding affinities with key protein targets, including peptide deformylase and β-carbonic anhydrase, with binding free energies (ΔG) ranging from −12.75 to −0.60 kcal/mol. CN exhibited exceptional activity against Staphylococcus epidermidis (29.6 ± 0.4 mm) and Candida albicans (36.6 ± 0.4 mm), supported by a significant binding affinity with β-carbonic anhydrase (ΔG: −5.23 kcal/mol). Dissociation constants (Kd) derived from MM-GBSA analyses indicated EU’s strong inhibitory potential with nano- to picomolar Kd values, directly correlating with low IC50 values. CN demonstrated moderate inhibitory activity with Kd in the micromolar range. Molecular dynamics (MD) simulations confirmed the stability of these protein–ligand complexes, revealing critical hydrophobic interactions, such as those involving PHE122, that contributed to binding stabilization. ADMET profiling further underscored the favorable pharmacokinetics and safety of both compounds. These findings establish EU and CN as promising candidates for antimicrobial therapy, with potential applications in combating MDR pathogens and biofilm-associated infections. The complementary strengths of EU and CN warrant further structural optimization and combination studies, offering new avenues in the development of next-generation antimicrobial agents.
The escalating issue of heavy metal (HM) contamination in agricultural soils presents an urgent c... more The escalating issue of heavy metal (HM) contamination in agricultural soils presents an urgent challenge to the sustainability of wheat (Triticum aestivum L.) production. This review underscores the critical need for innovative approaches to ensure food security while mitigating environmental degradation. The integration of nano and quantum technologies with multi-omics frameworks emerges as a groundbreaking solution to this pressing issue. HMs like Cd, As, and Pb severely impair plant physiology, leading to diminished yields and compromised grain quality. Nanoparticles such as ZnO, TiO₂, and MnO₂, along with quantum dots, have shown substantial promise in bolstering wheat's natural defense systems, enhancing both enzymatic and non-enzymatic antioxidant pathways, and reducing metal uptake through targeted detoxification mechanisms. By leveraging advanced omics technologies—transcriptomics, ionomics, proteomics, and metabolomics—researchers can unravel key molecular pathways and biomarkers, offering precision-guided interventions for metal stress management. Furthermore, future innovations like genome-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and transgenic techniques hold the potential to create wheat varieties inherently more resilient to environmental contaminants.. The review highlights the necessity of long-term field trials and the exploration of under-researched metals and nanoparticles to bring these promising laboratory findings to real-world application. These combined strategies not only contribute to sustainable agriculture but also provide a viable path toward reducing the ecological footprint of HM contamination, thereby safeguarding global food security.
Tridentate Schiff base ligand (L) was synthesized from reactions of N-phenyl-1,2-diaminobenzene a... more Tridentate Schiff base ligand (L) was synthesized from reactions of N-phenyl-1,2-diaminobenzene and 3-ethoxysalicylaldehyde. The Schiff base was hydrogenated by sodium borohydride to produce the second ligand (HL). Complexes with the general formula Pt(N^{NO})Cl were synthesized by reacting K2PtCl4 with the ligands in DMSO/ethanol mixtures, generating L-Pt and HL-Pt complexes. The ligand and its complex were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding of the platinum(II) compounds were evaluated by following changes induced on the viscosity of ct-DNA, indicating covalent binding mode with ct-DNA. L-Pt is strongly emissive with emission maximum ca. 630 nm, which complicated the evaluation of DNA- and BSA-binding by the fluorescence quenching technique. However, HL-Pt has good binding affinities with ct-DNA with apparent binding constant of 1.0 × 106 while BSA-binding studies indicated static quenching process with binding constant (Kb) value equals to 1.43 × 106. The half maximal inhibitory concentrations (IC50) values against MCF-7 and HepG2 suggest that L-Pt has better cytotoxic effect compared to that of HL-Pt and cisplatin. Although, both L-Pt and HL-Pt were more cytotoxic towards the normal cell line. The flow cytometry assay indicated that L-Pt, HL-Pt and cisplatin induce their cytotoxic effect by apoptosis. However, the cell cycle arrest of L-Pt and HL-Pt on MCF-7 show similar pattern but it is different to that of MCF-7 treated with cisplatin, suggesting different mechanism in activating the cell death. DFT calculations were employed to stimulate the binding of L-Pt and HL-Pt with a fragment of DNA (trimer), highlighting the effect of the ligands. In conclusion, the current study highlight the importance of the azomethine linkage in the ligand on the anticancer properties on the complexes of the type Pt(N^{NO})Cl.
Background/Objectives: The primary method used to pharmacologically arrest cancer development and... more Background/Objectives: The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despite intensive studies on new chemotherapeutics, the biggest problem remains the side effects associated with the inhibition of cell division in non-tumoural host cells. Methods: The efficacy and selectivity of the kojic acid derivative (L1) was studied in vitro with the use of tumoural (Caco2, SW480, HT29, T98G) and non- tumoural (HEK293T, RAW) cell lines. Light and electron microscopy observations were supported by the next generation sequencing (NGS), cytoflow, and spectroscopy analysis of mRNA and biomolecules, respectively. Results: The light and electron microscopy observations showed that L1 treatment leads to significant morphological changes in Caco2 cells, which are characteristic of mitosis arrest. Moreover, the fluorescent tubulin staining revealed the formation of tubulin ring structure associated with the apoptotic stage. Mitotic exit into apoptosis was further conformed by the cytoflow of early/late apoptosis stages and caspase-3 analysis. NGS investigation showed differentiated expressions of genes involved in mitosis and apoptosis processes. The observed IC50 in tumoural cell lines were as follows: Caco2 (IC50 = 68.2 mM), SW480 (IC50 = 15.5 mM), and HT29 (IC50 = 4.7 mM). Conclusions: The findings presented here suggest that L1 could be a valid candidate for oral prevention and/or chemotherapy in colorectal cancer. Considering high selectivity of L1 versus tumoural cell lines, more in-depth mechanistic studies could reveal unknown stages in carcinogenesis.
The novel complex of [Mn(SCN)2(neo)2], (1) was isolated at room temperature by mixing aqueous sol... more The novel complex of [Mn(SCN)2(neo)2], (1) was isolated at room temperature by mixing aqueous solutions of potassium thiocyanate and 2,9-dimethyl-1,10-phenanthroline (neocuproine) (neo) with that of manganese (II) chloride tetrahydrate. Complex 1 was fully described using FT-IR, UV–vis, and elemental analysis. The crystal structure of complex 1 was solved using single-crystal X-ray diffraction. The distorted octahedral geometry of Mn atom in complex 1 is caused by its chelation by two molecules of neocuproine ligands through four nitrogen atoms and two NCS anions in cis position. The discrete units of complex 1 assemble to create a 3D supramolecular network utilizing H-bonding and π-π stacking interactions. HepG2, HCT116, and MDA are three distinct cancer cell lines that were utilized to assess the anticancer activities of the newly developed complex 1. Using a normal cell line (MRC5), the cytotoxicity and selectivity of the designed complex 1 were assessed. A molecular docking investigation involving three cancer proteins and DNA is conducted to demonstrate the anticancer properties. Additionally, complex 1’s DNA binding ability was estimated using viscometric and spectroscopic methods. Lastly, the luminescence spectra of complex 1 and neocuproine were studied.
Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effec... more Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstanding use, contemporary biochemical and clinical research has identified curcumin—the primary active compound in turmeric—as possessing significant therapeutic potential. This review hypothesizes that curcumin’s antioxidant properties are pivotal in preventing and treating chronic inflammatory diseases, which are often precursors to more severe conditions, such as cancer, and neurological disorders, like Parkinson’s and Alzheimer’s disease. Additionally, while curcumin demonstrates a favorable safety profile, its anticoagulant effects warrant cautious application. This article synthesizes recent studies to elucidate the molecular mechanisms underlying curcumin’s actions and evaluates its therapeutic efficacy in various human illnesses, including cancer, inflammatory bowel disease, osteoarthritis, atherosclerosis, peptic ulcers, COVID-19, psoriasis, vitiligo, and depression. By integrating diverse research findings, this review aims to provide a comprehensive perspective on curcumin’s role in modern medicine and its potential as a multifaceted therapeutic agent.
The timely repair of injured skin is of outmost importance as the impaired wound healing may prov... more The timely repair of injured skin is of outmost importance as the impaired wound healing may provoke infections, formation of scarring tissues, and delayed wound closure. ThQ + Rut-loaded NC gel was produced using the ultrasonication nanoprecipitation technique and investigated for dermal wound healing. Formulations were characterized for particle size distribution, and ζ − potential, % drug entrapment, and % loading. The optimum NC gel was characterized for viscosity, spreadability, and gel texture. The optimized nanocrystal gel was produced and tested on fibroblast cell line and tested in vivo for healing assessment. The optimum particle size of obtained NC was 192 ± 2 nm, PDI of 0.201, with a ζ-potential of -9.9 ± 1.9 mV. Further, Rut and ThQ entrapment and loading from ThQ + Rut-loaded NC gel, were measured to 89 ± 0.9%, 85.7 ± 1.5%; 21 ± 2%, and 17.5 ± 2%. The NC gel showed viscosity of 1488 ± 0.12 mPa*s at shear rate of 40 (1/s). The hydrogel texture analysis revealed firmness, consistency and cohesiveness of 43.88 g, 208.19 g.sec, and − 15.88 g, respectively. The cell viability studies revealed that Rutin and ThQ in NC gel significantly enhanced proliferation of fibroblast cell vis-a-vis to drug suspensions (p < 0.01). The histopathology demonstrated that ThQ + Rut-loaded NC gel improved collagen formation and tissue remodelling towards wound healing compared with other treatment groups. Thus, we may conclude that Rut and ThQ from nanocrystal gel is safe and will improve the dermal wound healing process.
This study aimed to optimize MES-nanoparticles using Box Behnken Design (BBD) and investigate its... more This study aimed to optimize MES-nanoparticles using Box Behnken Design (BBD) and investigate its in vivo antioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose nanoparticle containing mesalamine has particles size of 142 ± 2.8 nm, zeta potential of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed nanoparticles has a uniform and spherical shape. The in-vitro release data disclosed that the ethyl cellulose nanoparticles containing mesalamine showed bursts release of 52±1.6% in simulated stomach media within 2 hours, followed by a steady release of 93±2.9% in simulated intestinal fluid that lasted for 48 hours. The mesalamine release from nanoparticle best match with the Korsmeyer-Peppas model (R2 = 0.962) and it followed fickian diffusion case I release mechanism. The formulation stability over six-months at 25 ± 2 °C with 65 ± 5% relative humidity, and 40 ± 2 °C with 75 ± 5% relative humidity showed no significant changes changes in colour, entrapment efficiency, particle sizes and zeta potential. As per in vivo results, MES-NP effectively increased GSH, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.
Adopting sustainable farming strategies that limit the reliance on synthetic fertilizers is criti... more Adopting sustainable farming strategies that limit the reliance on synthetic fertilizers is critical to maintain soil health and minimizing environmental impact. Cyanobacteria, tiny organisms capable of making their own food through photosynthesis, have the unique capability by transforming atmospheric nitrogen into ammonia or nitrate form that plants can utilize. This natural process makes them a valuable alternative for soil fertilization and enhancing plant growth. The study examines the role of nitrogen-fixing cyanobacteria for soil quality improvement and crop productivity. It highlights the mechanism by which these bacteria assimilates atmospheric nitrogen and make it available to plants, mainly in rice farming contexts. Additionally, this paper addresses the synergistic effects of integrating cyanobacteria with other beneficial bacteria to further enhance soil health and promote plant growth. It examines the challenges and opportunities associated with large-scale implementation of cyanobacterial fertilizers, including the choice of appropriate bacterial species and effective application strategies. The review also emphasis how genetic engineering and other advanced techniques are being used to improve cyanobacteria’s ability to fix nitrogen and improve stress tolerance. By compiling current research, this review provides a comprehensive overview of how these nitrogen-fixing cyanobacteria can support sustainable agriculture practices and suggests future research directions to make their use even more effective in various agricultural practices.
Simple Summary
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecti... more Simple Summary
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients.
Abstract
This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.
As photosynthetic microorganisms, cyanobacteria play a dominant part in numerous ecological syste... more As photosynthetic microorganisms, cyanobacteria play a dominant part in numerous ecological systems owing to their ability to fix carbon and nitrogen and are therefore an essential part of primary production in both aquatic and terrestrial environments. The utility of nitrogen-fixing cyanobacteria in plant biotechnology opens up promising strategies for the conservation and sustainable use of rare, endangered plant species and bioactive cell cultures. Here, we discuss the complicated physiological aspects of biological nitrogen fixation in cyanobacteria and their symbiotic relationship with plants. This review focuses on recent advances in biotechnological tools such as CRISPR-Cas9, nanotechnology and multiomics-based approaches for enhancing plant regeneration systems to cultivate specialized metabolites. We also look at the methods in vitro preservation of plants and how to scale up a culture using bioreactor systems. The review ends by highlighting the promise of cyanobacteria-powered plant biotechnology as a renewable mechanism for rare species conservation and specialized metabolites production, providing an optimistic modal, formative future direction in plant biosynthesis.
This study investigates potentially toxic elements (PTEs) concentrations in both washed and unwas... more This study investigates potentially toxic elements (PTEs) concentrations in both washed and unwashed leaves of Calotropis procera and in the soil near its roots along roadsides with varying vehicular traffic densities. Additionally, it explores the plant's physiological, biochemical, and morpho-anatomical responses to PTEs exposure. Samples of unwashed and washed leaves from roadside areas with very high, high, medium, and low traffic densities, as well as control sites located 100-500 meters away from roads, were analyzed for PTEs concentrations, physicochemical properties and morpho-anatomical characteristics. A paired sample t-test revealed significant differences (p<0.05) in PTEs concentrations, except for Mn, with higher levels in unwashed leaves compared to washed ones. The highest PTEs concentrations were observed in areas with very high traffic density (VHD), followed by high-density (HD), moderate (MD), and low-density (LD) areas. The study also explored the role of soil as a sink for these contaminants, revealing a strong positive correlation between vehicular density and PTEs level in soil. The bioaccumulation factor (BCF) indicated significant uptake of Pb, Cd, Cr, Mn, and Cu, with lower values for other elements. The study also assessed physiological and biochemical parameters, including chlorophyll content, ascorbic acid, antioxidant potential, and membrane stability index, all of which showed significant variations across sites with different traffic densities. Morphological and anatomical variations, such as reductions in leaf area, leaf thickness, and stomatal dimensions, were observed in polluted areas. Principal Component Analysis (PCA) highlighted the correlations between PTEs, morphological traits, and vehicular density, with notable negative effects at high traffic sites. In conclusion, C. procera is an effective phyto-accumulator and bioindicator of PTEs pollution, with high ecological adaptability, making it suitable for phytoremediation and pollution monitoring. This study highlights the impact of vehicular pollution on plant health and stresses the importance of monitoring these factors for environmental management.
Sulfated flavonoids, also named flavonoid sulfates, are a class of polyphenol derivatives from va... more Sulfated flavonoids, also named flavonoid sulfates, are a class of polyphenol derivatives from various plants often with a long history of use in traditional medicine around the world, that play an important role in secondary metabolism, chemical defense, and growth regulation of plants, and with significant and potential health benefits. Sulfated flavonoids are produced by a substitution reaction of a flavonoid moiety and a sulfate donor, where transfer of a sulfate group to hydroxyl groups in the flavonoid structure is catalyzed, either naturally or synthetically, by the enzyme sulfotransferase. Of note, several monocotyledonous and dicotyledonous plant families have been reported for their content of sulfated flavonoids. Various medically important bioactivities have been reported for sulfated flavonoids, including antitumor, antidiabetic, antimicrobial, and antiviral properties, and which we discuss in this review. The present review focuses on sulfated flavonoids extracted from plants but also discuss some chemically synthesized sulfated flavonoids explored, e.g., for their (potential) anticoagulant properties. This review aims to summarize the published data on naturally occurring and synthetic sulfated flavonoids, paying particular attention to their structural variations and occurrence, biosynthesis aspects, methods of identification, extraction and isolation, and biological activities. The review covers literature published in English, spanning the entire period from the first report in 1971 to January 2025. Finally, the current work emphasizes this class of compounds as a source of potential candidates for the development of new pharmaceutical drugs with beneficial bioactivities.
Synthesis and characterization of thymol-derived phenoxy acetamide derivatives using DFT, molecular docking, and parasitological investigations
Frontiers in Chemistry, 2025
Novel phenoxy acetamide derivatives based on a thymol moiety were synthesized for target parasito... more Novel phenoxy acetamide derivatives based on a thymol moiety were synthesized for target parasitological investigation. The newly synthesized compounds, 5a, 5b, 7a, 7b, and 9, were synthesized as phenoxy acetamide derivatives containing a phthalimide or naphthalimide ring through a condensation reaction with various acid anhydrides. Their structures were confirmed based on spectral data derived through Fourier-transform infrared, proton and carbon-13 nuclear magnetic resonance, and elemental analyses. The parasitological, biochemical, and immunological activities of the compounds were measured. The screened compounds were subjected to molecular docking in the active site of CpCDPK1, in addition to analyses based on Lipinski's rule and SwissADME. The results showed that compounds 5a, 5b, and 7b demonstrated promising antiparasitic activity, characterized by high gastrointestinal absorption and favorable drug-likeness profiles. Furthermore, 5a and 7b exhibited higher binding affinities than that of the reference drug. In practical assessments, compound 7b exhibited the highest percentage reduction in oocyst counts (67%). Density functional theory calculations were performed to assess the thermodynamic stability, molecular geometry, frontier molecular orbital energy gaps, and molecular electrostatic potentials of compounds 5a, 5b, 7a, 7b, and 9.Phenoxy acetamide derivatives based on a thymol moiety were synthesized through condensation reactions with a series of acid anhydrides. As shown in Scheme 1, 2-(2-isopropyl-5methylphenoxy)acetohydrazide (3) was reacted with different acid anhydrides, including phthalic anhydride (4a), 1,2,4-benzene tricarboxylic acid anhydride (4b), 1,8-naphthalic anhydride (6a), 4amino-1,8-naphthalic anhydride (6b), and pyromellitic dianhydride (8) in dimethylformamide (DMF) and glacial acetic acid under reflux conditions for 4-6 h to afford compounds 5a, 5b, 7a, 7b, and 9, respectively.The structures of the synthesized compounds 5a, 5b, 7a, 7b, and 9 were confirmed using spectroscopic data. The proton nuclear magnetic resonance ( 1 H-NMR) spectrum showed characteristic singlet peaks for NH (10.08-10.90 ppm) and aliphatic CH3 (1.13-2.27 ppm). The infrared (IR) spectra of all synthesized compounds showed two sharp bands of C=O (conjugated anhydride) at ν = 1792 cm -1 and 1744 cm -1 .
Naphthyl chalcone derivatives with a D-A-D architecture were designed and synthesized using Clais... more Naphthyl chalcone derivatives with a D-A-D architecture were designed and synthesized using Claisen-Schmidt condensation to explore their potential for optoelectronic applications, particularly in organic photovoltaics. Among the synthesized compounds, compounds 17 and 18 stood out due to their notable photophysical and electrochemical properties. The chalcones were characterized through photophysical and electrochemical analyses. Experimental results revealed significant absorption and emission in visible regions, with high Stokes shifts and favorable fluorescence quantum yields, especially for compounds 17 and 18. Cyclic voltammetry showed promising oxidation/reduction potentials, highlighting their charge transport capabilities. DFT and TD-DFT were used to investigate the electronic structure, molecular orbitals, optical properties, and electronic transitions. Computational analysis provided insights into frontier molecular orbitals, dipole moments, density of states, reactivity descriptors, charge transfer integrals and reorganization energy, molecular electrostatic potential, and transition density matrices. The findings demonstrate that these chalcones exhibit favorable optical properties and electrochemical characteristics, making them promising candidates for further experimental studies in OPV devices.
A novel platinum(IV) supramolecular complex; [PtCl 2 (2,2′-bipy) 2 ](PtCl 6) was synthesized in a... more A novel platinum(IV) supramolecular complex; [PtCl 2 (2,2′-bipy) 2 ](PtCl 6) was synthesized in aqueous acetonitrile solution at ambient temperature with constant stirring. The structure was confirmed by elemental analysis, FT-IR, UV-vis, NMR spectroscopy, and single-crystal X-ray diffraction, revealing a unique distorted octahedral geometry and a three-dimensional network stabilized by hydrogen bonding and π-π stacking. DNA binding studies, including electronic absorption titration and viscometry, indicated a groove binding mechanism with a binding constant (K b) of 5.00 × 10⁶ M-1. Molecular docking with DNA (PDB ID: 1BNA) and cancer-related proteins (PDB codes: 3ig7, 3eqm, 4fm9) supports these interactions, while in vitro anticancer assays demonstrated potent cytotoxicity with IC₅₀ values of 41.37 μM for HepG2, 47.62 μM for HCT116, and 73.90 μM for MDA-MB-231 cells, outperforming cisplatin in selectivity. This study not only advances our understanding of structure-activity relationships in platinum-based complexes but also highlights the potential of this complex as a promising candidate for developing more effective and less toxic anticancer agents.
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metaboli... more Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metabolic dysregulation, oxidative stress, amyloid-β (Aβ) aggregation, metal dyshomeostasis, and mitochondrial dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. This study investigates the metabolic effects of the alkaloids galantamine (GAL) and lycorine (LYC) in differentiated SH-SY5Y neuroblastoma cells, an established in vitro model for AD, which acquire a neuronal phenotype upon differentiation. Using untargeted and targeted NMR-based metabolomics combined with multivariate statistical analysis, we analyzed extracellular metabolic profiles under basal conditions and following Aβ42 exposure, both in the presence and absence of GAL and LYC. Our findings reveal distinct metabolic responses to Aβ toxicity, with significant alterations in pyruvate and glutamine metabolism. Both GAL and LYC contributed to the restoration of glutamine and lysine homeostasis, but LYC had a more pronounced effect, better sustaining cellular energy balance and mitochondrial function. Unlike LYC, GAL treatment was associated with pyruvate accumulation, highlighting a distinct metabolic response between the two compounds. These variations may reflect distinct mechanisms of action, potentially influencing their therapeutic roles in counteracting Aβ-induced toxicity. This study highlights the value of metabolic profiling for assessing neuroprotective agents and reinforces the potential of natural alkaloids in this context.
This study conducts a comprehensive metabolomic profiling of the Zygophyllum (Z) coccineum plant,... more This study conducts a comprehensive metabolomic profiling of the Zygophyllum (Z) coccineum plant, a halophyte prevalent in Saudi Arabia and Egypt, employing gas chromatography-mass spectrometry (GC–MS), liquid chromatography-mass spectrometry (LC–MS), and nuclear magnetic resonance (NMR) spectroscopy. Recognizing the plant’s significance in traditional medicine, we explore its adaptative mechanisms and potential pharmacological applications through the identification of metabolites. Various solvents, namely acetonitrile–water (AcW), isopropanol-methanol–water (IMW), and methanol–water (MW) were utilized for metabolite extraction. Our results reveal a diverse spectrum of metabolites, including amino acids, sugars, organic acids, alkaloids, steroids, and terpenoids, with significant variations in extraction efficiency and metabolite composition across solvents. Identified metabolites indicate the reason for using Z. coccineum leaves as traditional medicine in Saudi Arabia, and Egypt because of consist of several phytochemical metabolites used for the treatment of diabetes, kidney diseases, cancer, urinary tract secretions, dental pain, tumors, stomach pain, smallpox, asthma, rheumatism, gout, infections, hypertension, burns, and blood pressure, found in the extractions by the three different solvents on the analysis through GC/LC–MS spectrometry. Identified metabolites and their statistical analyses, including principal component analysis (PCA) and variable importance in projection (VIP), indicated that AcW in GC–MS provides a superior number of metabolites, clustering, and variability statistical analysis, while MW excels in LC–MS metabolic profiling and their statistical analysis compared to other solvents. These multilayers of solvents and analytical techniques approach underscores the importance of solvents in enhancing metabolomic studies, thereby facilitating a deeper understanding of the phytochemicals within Z. coccineum and their medicinal potential. Enhancing our knowledge of the plant’s metabolomics may inform future applications in pharmacology and agriculture.
Cancer presents a formidable and complex foe, standing as one of the foremost contributors to dis... more Cancer presents a formidable and complex foe, standing as one of the foremost contributors to disease-related fatalities across the globe. According to data from the Global Cancer Observatory (GLOBOCAN), projections indicate a staggering 28.4 million cases of cancer, encompassing both new diagnoses and deaths, by 2040. Therefore, developing effective and comprehensive treatment approaches for cancer patients is essential and the conventional approved treatments for cancers are associated with various harmful side effects. Our study aims to address the critical and widespread need for alternative therapies that can effectively combat cancer with minimal side effects.
The present contribution outlines a targeted approach using Lysine Specific Demethylase 1 (LSD1) to evaluate novel cyano-pyrimidine pendant chalcone derivatives as potential antiproliferative agents. Two sets of novel cyano-pyrimidine pendant chalcone derivatives were produced, and molecular docking was performed on the LSD1 protein. The ligands A1 and B1 belonging to series A and B, respectively, were found to have the highest docking scores of −11.095 and −10.773 kcal/mol, in that order. The ADME and toxicity studies of the ligands showed promising responses with respect to various pharmacokinetic and physicochemical parameters. The Molecular dynamics (MD) simulation results indicated effective diffusion of both complexes inside the protein cavity, facilitated by prominent interactions with various amino acids. Additionally, the complexes displayed high relative binding free energy. The computational screening of ligands indicates that ligands A1 and B1 exhibit potential for further exploration using various in vitro and in vivo techniques. These ligands may then serve as promising leads in the discovery of cancer drugs. The in-silico screening of the novel library of cyano-pyrimidine pendant chalcone derivatives was performed with a combination of molecular docking, MM-GBSA, ADME, toxicity and MD simulation. Molecular docking and MM-GBSA were conducted using the Glide and Prime tools, respectively, of the Schrödinger suite 12.8. The ligands were analysed for ADME using the Swiss ADME, while toxicity risks were evaluated using Osiris Property Explorer. Additionally, a 400ns MD simulation of LIGA1 and LIGB1 against the protein LSD1 was performed using the Desmond tool of Schrödinger suite 12.8 to validate the docking results and analyse the behaviour and stability of the complexes.
Background/Objectives: Although malaria is one of the oldest known human diseases, it continues t... more Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.
Repurposing eugenol and cinnamaldehyde as potent antimicrobial agents: A comprehensive in-vitro and in-silico study
Bioorganic Chemistry, 2025
Multi-drug-resistant (MDR) pathogens represent a critical global health threat, necessitating the... more Multi-drug-resistant (MDR) pathogens represent a critical global health threat, necessitating the development of novel antimicrobial agents with broad-spectrum activity and minimal toxicity. This study investigates the antimicrobial and anti-biofilm properties of 4-Allyl-2-methoxyphenol (eugenol, EU) and (E)-3-Phenylprop-2-enal (cinnamaldehyde, CN) against 19 clinically significant pathogens through a combination of in-vitro assays and in-silico analyses. EU displayed remarkable activity, particularly against Aspergillus niger (20.5 ± 0.5 mm), and strong binding affinities with key protein targets, including peptide deformylase and β-carbonic anhydrase, with binding free energies (ΔG) ranging from −12.75 to −0.60 kcal/mol. CN exhibited exceptional activity against Staphylococcus epidermidis (29.6 ± 0.4 mm) and Candida albicans (36.6 ± 0.4 mm), supported by a significant binding affinity with β-carbonic anhydrase (ΔG: −5.23 kcal/mol). Dissociation constants (Kd) derived from MM-GBSA analyses indicated EU’s strong inhibitory potential with nano- to picomolar Kd values, directly correlating with low IC50 values. CN demonstrated moderate inhibitory activity with Kd in the micromolar range. Molecular dynamics (MD) simulations confirmed the stability of these protein–ligand complexes, revealing critical hydrophobic interactions, such as those involving PHE122, that contributed to binding stabilization. ADMET profiling further underscored the favorable pharmacokinetics and safety of both compounds. These findings establish EU and CN as promising candidates for antimicrobial therapy, with potential applications in combating MDR pathogens and biofilm-associated infections. The complementary strengths of EU and CN warrant further structural optimization and combination studies, offering new avenues in the development of next-generation antimicrobial agents.
The escalating issue of heavy metal (HM) contamination in agricultural soils presents an urgent c... more The escalating issue of heavy metal (HM) contamination in agricultural soils presents an urgent challenge to the sustainability of wheat (Triticum aestivum L.) production. This review underscores the critical need for innovative approaches to ensure food security while mitigating environmental degradation. The integration of nano and quantum technologies with multi-omics frameworks emerges as a groundbreaking solution to this pressing issue. HMs like Cd, As, and Pb severely impair plant physiology, leading to diminished yields and compromised grain quality. Nanoparticles such as ZnO, TiO₂, and MnO₂, along with quantum dots, have shown substantial promise in bolstering wheat's natural defense systems, enhancing both enzymatic and non-enzymatic antioxidant pathways, and reducing metal uptake through targeted detoxification mechanisms. By leveraging advanced omics technologies—transcriptomics, ionomics, proteomics, and metabolomics—researchers can unravel key molecular pathways and biomarkers, offering precision-guided interventions for metal stress management. Furthermore, future innovations like genome-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and transgenic techniques hold the potential to create wheat varieties inherently more resilient to environmental contaminants.. The review highlights the necessity of long-term field trials and the exploration of under-researched metals and nanoparticles to bring these promising laboratory findings to real-world application. These combined strategies not only contribute to sustainable agriculture but also provide a viable path toward reducing the ecological footprint of HM contamination, thereby safeguarding global food security.
Tridentate Schiff base ligand (L) was synthesized from reactions of N-phenyl-1,2-diaminobenzene a... more Tridentate Schiff base ligand (L) was synthesized from reactions of N-phenyl-1,2-diaminobenzene and 3-ethoxysalicylaldehyde. The Schiff base was hydrogenated by sodium borohydride to produce the second ligand (HL). Complexes with the general formula Pt(N^{NO})Cl were synthesized by reacting K2PtCl4 with the ligands in DMSO/ethanol mixtures, generating L-Pt and HL-Pt complexes. The ligand and its complex were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding of the platinum(II) compounds were evaluated by following changes induced on the viscosity of ct-DNA, indicating covalent binding mode with ct-DNA. L-Pt is strongly emissive with emission maximum ca. 630 nm, which complicated the evaluation of DNA- and BSA-binding by the fluorescence quenching technique. However, HL-Pt has good binding affinities with ct-DNA with apparent binding constant of 1.0 × 106 while BSA-binding studies indicated static quenching process with binding constant (Kb) value equals to 1.43 × 106. The half maximal inhibitory concentrations (IC50) values against MCF-7 and HepG2 suggest that L-Pt has better cytotoxic effect compared to that of HL-Pt and cisplatin. Although, both L-Pt and HL-Pt were more cytotoxic towards the normal cell line. The flow cytometry assay indicated that L-Pt, HL-Pt and cisplatin induce their cytotoxic effect by apoptosis. However, the cell cycle arrest of L-Pt and HL-Pt on MCF-7 show similar pattern but it is different to that of MCF-7 treated with cisplatin, suggesting different mechanism in activating the cell death. DFT calculations were employed to stimulate the binding of L-Pt and HL-Pt with a fragment of DNA (trimer), highlighting the effect of the ligands. In conclusion, the current study highlight the importance of the azomethine linkage in the ligand on the anticancer properties on the complexes of the type Pt(N^{NO})Cl.
Background/Objectives: The primary method used to pharmacologically arrest cancer development and... more Background/Objectives: The primary method used to pharmacologically arrest cancer development and its metastasis is to disrupt the cell division process. There are a few approaches that may be used to meet this objective, mainly through inhibiting DNA replication or mitosis. Despite intensive studies on new chemotherapeutics, the biggest problem remains the side effects associated with the inhibition of cell division in non-tumoural host cells. Methods: The efficacy and selectivity of the kojic acid derivative (L1) was studied in vitro with the use of tumoural (Caco2, SW480, HT29, T98G) and non- tumoural (HEK293T, RAW) cell lines. Light and electron microscopy observations were supported by the next generation sequencing (NGS), cytoflow, and spectroscopy analysis of mRNA and biomolecules, respectively. Results: The light and electron microscopy observations showed that L1 treatment leads to significant morphological changes in Caco2 cells, which are characteristic of mitosis arrest. Moreover, the fluorescent tubulin staining revealed the formation of tubulin ring structure associated with the apoptotic stage. Mitotic exit into apoptosis was further conformed by the cytoflow of early/late apoptosis stages and caspase-3 analysis. NGS investigation showed differentiated expressions of genes involved in mitosis and apoptosis processes. The observed IC50 in tumoural cell lines were as follows: Caco2 (IC50 = 68.2 mM), SW480 (IC50 = 15.5 mM), and HT29 (IC50 = 4.7 mM). Conclusions: The findings presented here suggest that L1 could be a valid candidate for oral prevention and/or chemotherapy in colorectal cancer. Considering high selectivity of L1 versus tumoural cell lines, more in-depth mechanistic studies could reveal unknown stages in carcinogenesis.
The novel complex of [Mn(SCN)2(neo)2], (1) was isolated at room temperature by mixing aqueous sol... more The novel complex of [Mn(SCN)2(neo)2], (1) was isolated at room temperature by mixing aqueous solutions of potassium thiocyanate and 2,9-dimethyl-1,10-phenanthroline (neocuproine) (neo) with that of manganese (II) chloride tetrahydrate. Complex 1 was fully described using FT-IR, UV–vis, and elemental analysis. The crystal structure of complex 1 was solved using single-crystal X-ray diffraction. The distorted octahedral geometry of Mn atom in complex 1 is caused by its chelation by two molecules of neocuproine ligands through four nitrogen atoms and two NCS anions in cis position. The discrete units of complex 1 assemble to create a 3D supramolecular network utilizing H-bonding and π-π stacking interactions. HepG2, HCT116, and MDA are three distinct cancer cell lines that were utilized to assess the anticancer activities of the newly developed complex 1. Using a normal cell line (MRC5), the cytotoxicity and selectivity of the designed complex 1 were assessed. A molecular docking investigation involving three cancer proteins and DNA is conducted to demonstrate the anticancer properties. Additionally, complex 1’s DNA binding ability was estimated using viscometric and spectroscopic methods. Lastly, the luminescence spectra of complex 1 and neocuproine were studied.
Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effec... more Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstanding use, contemporary biochemical and clinical research has identified curcumin—the primary active compound in turmeric—as possessing significant therapeutic potential. This review hypothesizes that curcumin’s antioxidant properties are pivotal in preventing and treating chronic inflammatory diseases, which are often precursors to more severe conditions, such as cancer, and neurological disorders, like Parkinson’s and Alzheimer’s disease. Additionally, while curcumin demonstrates a favorable safety profile, its anticoagulant effects warrant cautious application. This article synthesizes recent studies to elucidate the molecular mechanisms underlying curcumin’s actions and evaluates its therapeutic efficacy in various human illnesses, including cancer, inflammatory bowel disease, osteoarthritis, atherosclerosis, peptic ulcers, COVID-19, psoriasis, vitiligo, and depression. By integrating diverse research findings, this review aims to provide a comprehensive perspective on curcumin’s role in modern medicine and its potential as a multifaceted therapeutic agent.
The timely repair of injured skin is of outmost importance as the impaired wound healing may prov... more The timely repair of injured skin is of outmost importance as the impaired wound healing may provoke infections, formation of scarring tissues, and delayed wound closure. ThQ + Rut-loaded NC gel was produced using the ultrasonication nanoprecipitation technique and investigated for dermal wound healing. Formulations were characterized for particle size distribution, and ζ − potential, % drug entrapment, and % loading. The optimum NC gel was characterized for viscosity, spreadability, and gel texture. The optimized nanocrystal gel was produced and tested on fibroblast cell line and tested in vivo for healing assessment. The optimum particle size of obtained NC was 192 ± 2 nm, PDI of 0.201, with a ζ-potential of -9.9 ± 1.9 mV. Further, Rut and ThQ entrapment and loading from ThQ + Rut-loaded NC gel, were measured to 89 ± 0.9%, 85.7 ± 1.5%; 21 ± 2%, and 17.5 ± 2%. The NC gel showed viscosity of 1488 ± 0.12 mPa*s at shear rate of 40 (1/s). The hydrogel texture analysis revealed firmness, consistency and cohesiveness of 43.88 g, 208.19 g.sec, and − 15.88 g, respectively. The cell viability studies revealed that Rutin and ThQ in NC gel significantly enhanced proliferation of fibroblast cell vis-a-vis to drug suspensions (p < 0.01). The histopathology demonstrated that ThQ + Rut-loaded NC gel improved collagen formation and tissue remodelling towards wound healing compared with other treatment groups. Thus, we may conclude that Rut and ThQ from nanocrystal gel is safe and will improve the dermal wound healing process.
This study aimed to optimize MES-nanoparticles using Box Behnken Design (BBD) and investigate its... more This study aimed to optimize MES-nanoparticles using Box Behnken Design (BBD) and investigate its in vivo antioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose nanoparticle containing mesalamine has particles size of 142 ± 2.8 nm, zeta potential of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed nanoparticles has a uniform and spherical shape. The in-vitro release data disclosed that the ethyl cellulose nanoparticles containing mesalamine showed bursts release of 52±1.6% in simulated stomach media within 2 hours, followed by a steady release of 93±2.9% in simulated intestinal fluid that lasted for 48 hours. The mesalamine release from nanoparticle best match with the Korsmeyer-Peppas model (R2 = 0.962) and it followed fickian diffusion case I release mechanism. The formulation stability over six-months at 25 ± 2 °C with 65 ± 5% relative humidity, and 40 ± 2 °C with 75 ± 5% relative humidity showed no significant changes changes in colour, entrapment efficiency, particle sizes and zeta potential. As per in vivo results, MES-NP effectively increased GSH, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.
Adopting sustainable farming strategies that limit the reliance on synthetic fertilizers is criti... more Adopting sustainable farming strategies that limit the reliance on synthetic fertilizers is critical to maintain soil health and minimizing environmental impact. Cyanobacteria, tiny organisms capable of making their own food through photosynthesis, have the unique capability by transforming atmospheric nitrogen into ammonia or nitrate form that plants can utilize. This natural process makes them a valuable alternative for soil fertilization and enhancing plant growth. The study examines the role of nitrogen-fixing cyanobacteria for soil quality improvement and crop productivity. It highlights the mechanism by which these bacteria assimilates atmospheric nitrogen and make it available to plants, mainly in rice farming contexts. Additionally, this paper addresses the synergistic effects of integrating cyanobacteria with other beneficial bacteria to further enhance soil health and promote plant growth. It examines the challenges and opportunities associated with large-scale implementation of cyanobacterial fertilizers, including the choice of appropriate bacterial species and effective application strategies. The review also emphasis how genetic engineering and other advanced techniques are being used to improve cyanobacteria’s ability to fix nitrogen and improve stress tolerance. By compiling current research, this review provides a comprehensive overview of how these nitrogen-fixing cyanobacteria can support sustainable agriculture practices and suggests future research directions to make their use even more effective in various agricultural practices.
Simple Summary
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecti... more Simple Summary
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients.
Abstract
This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.
As photosynthetic microorganisms, cyanobacteria play a dominant part in numerous ecological syste... more As photosynthetic microorganisms, cyanobacteria play a dominant part in numerous ecological systems owing to their ability to fix carbon and nitrogen and are therefore an essential part of primary production in both aquatic and terrestrial environments. The utility of nitrogen-fixing cyanobacteria in plant biotechnology opens up promising strategies for the conservation and sustainable use of rare, endangered plant species and bioactive cell cultures. Here, we discuss the complicated physiological aspects of biological nitrogen fixation in cyanobacteria and their symbiotic relationship with plants. This review focuses on recent advances in biotechnological tools such as CRISPR-Cas9, nanotechnology and multiomics-based approaches for enhancing plant regeneration systems to cultivate specialized metabolites. We also look at the methods in vitro preservation of plants and how to scale up a culture using bioreactor systems. The review ends by highlighting the promise of cyanobacteria-powered plant biotechnology as a renewable mechanism for rare species conservation and specialized metabolites production, providing an optimistic modal, formative future direction in plant biosynthesis.
Metabolic Dynamics in Host-Microbe Interaction, 2025
Metabolic dynamics in attack and defense mechanisms are fascinating topics that illustrate the co... more Metabolic dynamics in attack and defense mechanisms are fascinating topics that illustrate the complex ways organisms adapt to their environments. Attack mechanisms involve several functions, including energy production and metabolic adaptation, where some organisms change their appearance or behavior to balance into their environment. Defense mechanisms involve stress response, immune system activation, repair, and recovery. This chapter provides an overview of the methods applied in modern metabolomics, including single-cell metabolomics and targeted/untargeted approaches, emphasizing how metabolite production rapidly shifts in response to environmental and cellular changes. To effectively monitor these spontaneous effects, it is essential to conduct metabolomics studies with a carefully controlled experimental design. This includes meticulous sample collection, efficient metabolite extraction, and optimization of parameters for the most relevant analytical platform. This chapter outlines the most relevant and commonly used methods for metabolite extraction, aiming to maximize the number of metabolites recovered. This is followed by a summary of the advantages and limitations of the most frequently employed analytical tools, with a particular focus on nuclear magnetic resonance (NMR) and various types of mass spectrometry (MS). Finally, we emphasize the importance of integrating different omics sciences to achieve a comprehensive understanding of biological systems.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this p... more The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Harnessing Crop Biofortification for Sustainable Agriculture, 2024
Biofortification of leafy vegetables is a crucial strategy for enhancing their nutritional profil... more Biofortification of leafy vegetables is a crucial strategy for enhancing their nutritional profile to address widespread nutrient deficiencies and promote human well-being. Leafy greens like as spinach, kale, asparagus, and lettuce are rich in essential vitamins, minerals, and phytochemicals, which serve as indispensable sources of nutrition. However, they often lack sufficient levels of key nutrients, especially in regions with narrow food diversity. The cumulative interest regarding enrichment of leafy vegetables with mineral nutrients has motivated research communities to find better viable and economical techniques regarding fortification of vegetables. Researchers employed various techniques in biofortification to improve the nutritional status of leafy vegetables, with the focus on increasing vital micronutrients such as zinc, silicon, magnesium, potassium, iodine, and folate. The benefits of biofortified leafy vegetables extend beyond addressing individual nutrient deficiencies, playing a crucial role in combating malnutrition, particularly in vulnerable populations like children and pregnant women and their regular consumption promotes overall well-being, immunity, and cognitive development, as well as reduce the risk of chronic diseases. Furthermore, biofortification aligns with sustainable agriculture practices, promoting crop resilience, reducing reliance on synthetic fertilizers, and enhancing food security. By maximizing the nutritional potential of leafy vegetables, and investing in research, biofortification offers a cost-effective and scalable solution to address malnutrition and promoting sustainable development worldwide. Furthermore, it is imperative for the policy makers to overcome the research gap by providing awareness among community regarding adoption of natural biofortified vegetables.
Surgery, chemotherapy, and radiation are standard cancer therapies to remove or kill cancer cells... more Surgery, chemotherapy, and radiation are standard cancer therapies to remove or kill cancer cells. These therapies can successfully treat cancer in its early stages but are typically less effective at advanced stages or recurrence. The past few decades have led to a fourth therapy, cancer immunotherapy. Among the immunotherapy approaches for tumors is cancer vaccination. Cancer vaccines can stimulate immunity against tumors through tumor antigens. Ideal cancer vaccines stimulate both cellular and humoral immunity while overcoming tumor-immune suppression to stop tumor growth and eventually kill tumor cells. Cancer vaccines are different from conventional vaccines since their therapeutic goals involve triggering tumor antigen-specific cellular immune responses to destroy the tumor cells. Additionally, tumor antigens are endogenous and have limited immunogenicity, unlike conventional vaccinations that use antigens from exogenous infections.
Although the identification and characterization of several tumor antigens have led to the creation of numerous antigen-derived cancer vaccines, many vaccines lack clinical effectiveness because they are insufficiently immunogenic. Therefore, adjuvants are used in vaccination formulations to promote potent and durable immune responses. In this chapter, we summarize the current standard cancer treatment modalities, highlight the present state of cancer immunotherapy, and describe many platforms and optimization techniques for cancer vaccines.
Metabolomics: A Path Towards Personalized Medicine, 2023
Over the course of years healthcare systems have utilized various '-omics' approaches to prognose... more Over the course of years healthcare systems have utilized various '-omics' approaches to prognose, diagnose and evaluate the treatment efficacy of cancer diseases. Metabolomics is one of the latest prominent additions to the-omics approaches, characterized by its versatile methodology. Owing to constant improvements in the field, a metabolomic aims to provide a faster and a more accurate diagnosis, as well as personalized and optimal strategies of treatment. In recent years, a growing number of studies have utilized metabolomics approach to find new disease-related biomarkers of cancer diseases. Here we present the summary of recent advances in biomarker discovery for various types of cancers such as leukemia, ovarian, lung, breast and liver cancers as well as cancer-related cachexia.
Nuclear magnetic resonance (NMR) is one of the most common and powerful techniques used in metabo... more Nuclear magnetic resonance (NMR) is one of the most common and powerful techniques used in metabolomics. The inherent quantitative, nondestructive, and nonbiased properties, together with minimal sample preparation/manipulation make NMR a potent approach to any investigative metabolic study involving biological systems. NMR spectroscopy offers several unique monitoring opportunities such as extremely high reproducibility, relatively short experiment times, a wide range of available experiments (e.g., multidimensional and multinuclear based), and advanced highly automated robotic sample handling/exchange technologies enabling potentially hundreds of samples per instrument in a single day.
In this chapter, we highlight the primary advantages and limitations of NMR spectroscopy, introduce the most commonly applied NMR experiments in metabolomics, and review some of the recent advances with selected examples of novel applications, such as high-resolution magic-angle spinning for tissue samples, and pure shift NMR method as an example of a promising new approach that can be used to overcome the overlapping of 1D NMR spectra. The main advantages of NMR spectroscopy with a particular focus on reproducibility are also presented.
NMR Spectroscopy for Probing Functional Dynamics at Biological Interfaces , 2022
Structural biology has come a long way since the first inception of multidimensional NMR. The dip... more Structural biology has come a long way since the first inception of multidimensional NMR. The dipole-dipole interaction between two spatially closed spins provides a powerful tool to probe macromolecules' three-dimensional (3D) structure, such as proteins. However, the main challenge for macromolecules is to assign the NMR chemical shifts of all signals of the investigated protein. This chapter presents different 3D triple resonance NMR experiments dedicated to assignments of NMR signals of protein backbone structure. In addition, the through-space correlation experiments, namely NOESY, ROESY, and HOESY, are presented with detailed information about the advantages and limitations of each. The main strength of NMR lies in obtaining molecular structures under natural conditions and detailed information on the molecular dynamics at different timescales. The detailed characterization of sub-nanosecond segmental motions in proteins was characterized long before the advent of the first solution structure by NMR. Herein, the basic concept behind structure determination and elucidating protein dynamics on different timescales is presented. This book chapter will also highlight the NMR methodologies regarding characterizing sparsely populated protein conformations and transient states, vital for macromolecular functions.
Metabolomics - Methodology and Applications in Medical Sciences and Life Sciences, 2021
Pharmacology is the predominant first-line treatment for most pathologies. However, various facto... more Pharmacology is the predominant first-line treatment for most pathologies. However, various factors, such as genetics, gender, diet, and health status, significantly influence the efficacy of drugs in different patients, sometimes with fatal consequences. Personalized diagnosis substantially improves treatment efficacy but requires a more comprehensive process for health assessment. Pharmacometabolomics combines metabolomic, genomic, transcriptomic and proteomic approaches and therefore offers data that other analytical methods cannot provide. In this way, pharmacometabolomics more accurately guides medical professionals in predicting an individual's response to selected drugs. In this chapter, we discuss the potentials and the advantages of metabolomics approaches for designing innovative and personalized drug treatments.
Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, ... more Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported methods that enable quick acquisition of NMR spectra, as well as new methods of faster, efficient, and informative two-dimensional (2D) NMR methods. Fast and efficient data acquisition has risen in response to an increasing need to investigate chemical and biological processes in real time. Several new techniques have been successfully introduced. One example of this is band-selective optimized-flip-angle short-transient (SOFAST) NMR, which has opened the door to studying the kinetics of biological processes such as the phosphorylation of proteins. The fast recording of NMR spectra allows researchers to investigate time sensitive molecules that have limited stability under experimental conditions. The increasing awareness that molecular structures are dynamic, rather than static, has pushed some researchers to find alternatives to standard, time-consuming methods of 15 N relaxation observ-ables acquisition.
Uploads
Papers by Mariusz Jaremko
The present contribution outlines a targeted approach using Lysine Specific Demethylase 1 (LSD1) to evaluate novel cyano-pyrimidine pendant chalcone derivatives as potential antiproliferative agents. Two sets of novel cyano-pyrimidine pendant chalcone derivatives were produced, and molecular docking was performed on the LSD1 protein. The ligands A1 and B1 belonging to series A and B, respectively, were found to have the highest docking scores of −11.095 and −10.773 kcal/mol, in that order. The ADME and toxicity studies of the ligands showed promising responses with respect to various pharmacokinetic and physicochemical parameters. The Molecular dynamics (MD) simulation results indicated effective diffusion of both complexes inside the protein cavity, facilitated by prominent interactions with various amino acids. Additionally, the complexes displayed high relative binding free energy. The computational screening of ligands indicates that ligands A1 and B1 exhibit potential for further exploration using various in vitro and in vivo techniques. These ligands may then serve as promising leads in the discovery of cancer drugs. The in-silico screening of the novel library of cyano-pyrimidine pendant chalcone derivatives was performed with a combination of molecular docking, MM-GBSA, ADME, toxicity and MD simulation. Molecular docking and MM-GBSA were conducted using the Glide and Prime tools, respectively, of the Schrödinger suite 12.8. The ligands were analysed for ADME using the Swiss ADME, while toxicity risks were evaluated using Osiris Property Explorer. Additionally, a 400ns MD simulation of LIGA1 and LIGB1 against the protein LSD1 was performed using the Desmond tool of Schrödinger suite 12.8 to validate the docking results and analyse the behaviour and stability of the complexes.
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients.
Abstract
This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.
The present contribution outlines a targeted approach using Lysine Specific Demethylase 1 (LSD1) to evaluate novel cyano-pyrimidine pendant chalcone derivatives as potential antiproliferative agents. Two sets of novel cyano-pyrimidine pendant chalcone derivatives were produced, and molecular docking was performed on the LSD1 protein. The ligands A1 and B1 belonging to series A and B, respectively, were found to have the highest docking scores of −11.095 and −10.773 kcal/mol, in that order. The ADME and toxicity studies of the ligands showed promising responses with respect to various pharmacokinetic and physicochemical parameters. The Molecular dynamics (MD) simulation results indicated effective diffusion of both complexes inside the protein cavity, facilitated by prominent interactions with various amino acids. Additionally, the complexes displayed high relative binding free energy. The computational screening of ligands indicates that ligands A1 and B1 exhibit potential for further exploration using various in vitro and in vivo techniques. These ligands may then serve as promising leads in the discovery of cancer drugs. The in-silico screening of the novel library of cyano-pyrimidine pendant chalcone derivatives was performed with a combination of molecular docking, MM-GBSA, ADME, toxicity and MD simulation. Molecular docking and MM-GBSA were conducted using the Glide and Prime tools, respectively, of the Schrödinger suite 12.8. The ligands were analysed for ADME using the Swiss ADME, while toxicity risks were evaluated using Osiris Property Explorer. Additionally, a 400ns MD simulation of LIGA1 and LIGB1 against the protein LSD1 was performed using the Desmond tool of Schrödinger suite 12.8 to validate the docking results and analyse the behaviour and stability of the complexes.
Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients.
Abstract
This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.
Although the identification and characterization of several tumor antigens have led to the creation of numerous antigen-derived cancer vaccines, many vaccines lack clinical effectiveness because they are insufficiently immunogenic. Therefore, adjuvants are used in vaccination formulations to promote potent and durable immune responses. In this chapter, we summarize the current standard cancer treatment modalities, highlight the present state of cancer immunotherapy, and describe many platforms and optimization techniques for cancer vaccines.
In this chapter, we highlight the primary advantages and limitations of NMR spectroscopy, introduce the most commonly applied NMR experiments in metabolomics, and review some of the recent advances with selected examples of novel applications, such as high-resolution magic-angle spinning for tissue samples, and pure shift NMR method as an example of a promising new approach that can be used to overcome the overlapping of 1D NMR spectra. The main advantages of NMR spectroscopy with a particular focus on reproducibility are also presented.