The arrival of comprehensive genome sequencing has accelerated the understanding of genetically a... more The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemotherapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-inclass covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.
Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts ... more Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts to discover novel antiparkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative stress in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of 2-chloro,5-trifluoromethyl substituted analog, halogen substituted derivatives exhibited moderate antiparkinsonian activity. The results of biochemical investigations from brain homogenate of mice outline the importance of neuroprotective/antioxidant therapy for Parkinson's disease (PD), supporting the notion that the oxidative stress may play a significant role in the pathophysiological mechanisms underlying PD. Molecular docking studies of these compounds with adenosine A(2A) receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human A(2A) receptor for the design and development of potent antagonists. Parameters for Lipinski's rule of 5 were calculated computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties of a compound. None of the synthesized compounds violated Lipinski's rule, making them suitable drug candidate for the treatment of PD.
The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action t... more The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action through full agonistic activity on PPAR-γ receptors. Full agonists are known for the side effect of weight gain, while partial agonists are weak to non-adipogenic compounds possessing anti-diabetic property. This work identified a new synthetic oxadiazolyl thiazolidinedione (OXTZD) as a ligand for PPAR-γ receptor with partial agonist activity and less transactivation potential compared to rosiglitazone through in-vitro PPAR-γ competitive binding assay and PPAR-γ transactivation-based luciferase reporter assay, respectively. OXTZD did not induce significant lipid accumulation when compared to differentiation control which contained insulin in PPAR-γ-dependent adipogenesis assay. In-vivo studies have proved that OXTZD effectively reduced blood glucose level in type 2 diabetic rats and also improved glucose tolerance and insulin sensitivity. After 15 days of oral treatment with OXTZD, rats did not gain weight, suggesting that OXTZD was effective in suppressing the weight gain. Molecular docking of OXTZD to PPAR-γ, predicted hydrogen bonds with SER342, ARG288, and CYS285 residues in arm III of the ligand binding domain which are unique to the partial agonists. Results of in-vitro, in-vivo, and docking studies were in good correlation to the fact that OXTZD is a PPAR-γ partial agonist having glucose-lowering property and lacks the side effect of weight gain. In conclusion, OXTZD could be developed as a therapeutic agent for diabetes and/or serve as a lead compound for further drug design studies targeting PPAR-γ for effective management of type 2 diabetes without inducing weight gain.
Design of novel PPAR-γ modulators with better binding efficiency and fewer side effects to treat ... more Design of novel PPAR-γ modulators with better binding efficiency and fewer side effects to treat type 2 diabetes is still a challenge for medicinal chemists. Cost and time efficient computational methods have presently become an integral part of research in nuclear receptors and their ligands, enabling hit to lead identification and lead optimization. This review will focus on cutting-edge technologies used in most recent studies on the design of PPAR- γ agonists and will discuss the chemistry of a few molecules which emerged successful. Virtual screening of natural product libraries is an effective strategy to harness nature as the source of ligands for PPARs. Databases of natural products, drug molecules, and chemical substances facilitate this approach, where these molecules are virtually screened by similarity search, ADMETox properties, pharmacophore modelling and shape-based modelling. Docking is a valuable in-silico approach to probe the PPAR-ligand interaction. Rigid docking of ligands with various crystallized structures of the PPARs is a routinely used model. Induced fit docking and core hopping approach in docking were reported as rapid screening methods to identify novel leads and to predict the PPAR- γ and PPAR-α/ γ dual agonistic activity. One-dimensional drug profile matching is one of the recent virtual screening methods by which an antiprotozoal drug, Nitazoxanide, was identified as a PPAR- γ agonist. Virtual screening workflow can be customized by choosing appropriate models and applying them either sequentially or simultaneously to achieve convincing and reliable results.
Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is ... more Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, β-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the a...
UV-spectrophotometric determination of dissociation constant (pKa) is used routinely in various r... more UV-spectrophotometric determination of dissociation constant (pKa) is used routinely in various research fields. This review highlights the structural attributes of organic compounds that exhibit distinct pH-sensitive UV-absorbance for ionized and unionized species qualifying for pKa measurement. Organic compounds must possess a double bond, the chromophore adjacent to the ionizing functional group. Compounds bearing up to five sigma bonds between the chromophore and ionizing group are eligible for UV-spectrophotometric determination of pKa. This review serves as a quick guide for knowledge about structural requirements expediting pKa determination by UV-spectrophotometry. Besides, the study also identified the gap in research on pKa in drug discovery and food chemistry, revealing the necessity of determining pKa at the early stages of drug and food research to enhance the success rate in their development.
International Journal of Medicinal Chemistry, 2017
Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. ... more Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogue...
Watercress oil (WCO) is the seed oil of Nasturtium officinale, Brassicaceae family. WCO is a cosm... more Watercress oil (WCO) is the seed oil of Nasturtium officinale, Brassicaceae family. WCO is a cosmetic for hair growth approved by the Saudi Food and Drug Authority (SFDA). The study aimed to analyze by GC–MS, the phytochemical profile and the safety of WCO as a cosmetic according to SFDA, validates the traditional method of applying hot oil mixtures to the scalp, and also reports the pH, UV absorption, and in-silico binding mechanism of fatty acids for hair growth. The absorption of UV-B light (284.50 nm and 290.60 nm) by WCO suggests that it acts as a sunscreen for the scalp. The pH of the marketed WCO, 5.53 ± 0.02, shall not damage the scalp and hair. The GC–MS analysis confirmed fatty acids as the principal constituents (65.65%) of WCO composed of monounsaturated fatty acids (MUFAs): cis-11-Octadecenoic acid (17.14%), cis-9-Octadecenoic acid (17.11%), cis-13-Eicosenoic acid (11.13%), cis-11-Eicosenoic acid (3.48%), and cis-13-Docosenoic acid (1.64%); saturated fatty acid: n-Hexad...
Purpose: To develop a high performance thin-layer chromatography (HPTLC procedure for quantitatio... more Purpose: To develop a high performance thin-layer chromatography (HPTLC procedure for quantitation of apigenin in ethanol extract of Matricaria chamomilla (Babunaj) flowers, and to evaluate the extract for in vitro cytotoxic effect on MCF-7 cell lines. Methods: Quantification of apigenin was carried out using a CAMAG TLC system. A combination of toluene, ethyl acetate and formic acid (4.5:3.5:0.2 v/v/v) was used as mobile phase, with densitometry detection at 336 nm. The HPTLC procedure was subjected to validation as per ICH guidelines. The cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: A sharp apigenin band at Rf of 0.51 was obtained, and the content of apigenin in the extract was 0.062 % w/w. The detection limit (LOD) and quantification limit (LOQ) were 0.19 and 0.57 ng/band, respectively. MTT assay results indicate that M. chamomilla was cytotoxic to Michigan Cancer Foundation-7 (MCF-7) cells, with h...
Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric k... more Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric kernel and lipid/lipid–PEG shells that have the physical stability and biocompatibility of both polymeric nanoparticles and liposomes. PLNs have emerged as a highly potent and promising nanocarrier for a variety of biomedical uses, including drug delivery and biomedical imaging, owing to recent developments in nanomedicine. In contrast with other forms of drug delivery systems, PLNs have been regarded as seamless and stable because they are simple to prepare and exhibit excellent stability. Natural, semi-synthetic, and synthetic polymers have been used to make these nanocarriers. Due to their small scale, PLNs can be used in a number of applications, including anticancer therapy, gene delivery, vaccine delivery, and bioimaging. These nanoparticles are also self-assembled in a reproducible and predictable manner using a single or two-step nanoprecipitation process, making them significantl...
Computational assessment of the binding interactions of drugs is an important component of comput... more Computational assessment of the binding interactions of drugs is an important component of computer-aided drug design paradigms. In this perspective, a set of 30 1-(substituted phenyl)-3-(naphtha[1, 2-d] thiazol-2-yl) urea/thiourea derivatives showing antiparkinsonian activity were docked into inhibitor binding cavity of human adenosine A2A receptor (AA2AR) to understand their mode of binding interactions in silico. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results signify that the molecular docking approach is reliable and produces a good correlation coefficient (r2 = 0.483) between docking score and antiparkinsonian activity (in terms of % reduction in catalepsy score). Potent antiparkinsonian agents carried methoxy group in the phenyl ring, exhibited both hydrophilic and lipophilic interactions with lower energy of binding at the AA2AR. These molecular docking analyses should, in our view, contribute for further ...
Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified p... more Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide...
Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial a... more Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4- thiazolidinedione is a structural scaffold that contains pharmacophores similar to β-lactam and non- β-lactam antibiotics. The objective of the study was to synthesize newer 3,5-disubstituted-2,4-thiazolidinediones (DTZDs) and subject them to in-vitro antibacterial screening against bacterial pathogens. Also, we performed in-silico docking of selected compounds to penicillin-binding proteins and beta-lactamases. Methods: Intermediate Schiff bases were prepared by reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zone...
The arrival of comprehensive genome sequencing has accelerated the understanding of genetically a... more The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemotherapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-inclass covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.
Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts ... more Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts to discover novel antiparkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative stress in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of 2-chloro,5-trifluoromethyl substituted analog, halogen substituted derivatives exhibited moderate antiparkinsonian activity. The results of biochemical investigations from brain homogenate of mice outline the importance of neuroprotective/antioxidant therapy for Parkinson's disease (PD), supporting the notion that the oxidative stress may play a significant role in the pathophysiological mechanisms underlying PD. Molecular docking studies of these compounds with adenosine A(2A) receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human A(2A) receptor for the design and development of potent antagonists. Parameters for Lipinski's rule of 5 were calculated computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties of a compound. None of the synthesized compounds violated Lipinski's rule, making them suitable drug candidate for the treatment of PD.
The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action t... more The familiar glitazone anti-diabetics are thiazolidinedione derivatives, known to elicit action through full agonistic activity on PPAR-γ receptors. Full agonists are known for the side effect of weight gain, while partial agonists are weak to non-adipogenic compounds possessing anti-diabetic property. This work identified a new synthetic oxadiazolyl thiazolidinedione (OXTZD) as a ligand for PPAR-γ receptor with partial agonist activity and less transactivation potential compared to rosiglitazone through in-vitro PPAR-γ competitive binding assay and PPAR-γ transactivation-based luciferase reporter assay, respectively. OXTZD did not induce significant lipid accumulation when compared to differentiation control which contained insulin in PPAR-γ-dependent adipogenesis assay. In-vivo studies have proved that OXTZD effectively reduced blood glucose level in type 2 diabetic rats and also improved glucose tolerance and insulin sensitivity. After 15 days of oral treatment with OXTZD, rats did not gain weight, suggesting that OXTZD was effective in suppressing the weight gain. Molecular docking of OXTZD to PPAR-γ, predicted hydrogen bonds with SER342, ARG288, and CYS285 residues in arm III of the ligand binding domain which are unique to the partial agonists. Results of in-vitro, in-vivo, and docking studies were in good correlation to the fact that OXTZD is a PPAR-γ partial agonist having glucose-lowering property and lacks the side effect of weight gain. In conclusion, OXTZD could be developed as a therapeutic agent for diabetes and/or serve as a lead compound for further drug design studies targeting PPAR-γ for effective management of type 2 diabetes without inducing weight gain.
Design of novel PPAR-γ modulators with better binding efficiency and fewer side effects to treat ... more Design of novel PPAR-γ modulators with better binding efficiency and fewer side effects to treat type 2 diabetes is still a challenge for medicinal chemists. Cost and time efficient computational methods have presently become an integral part of research in nuclear receptors and their ligands, enabling hit to lead identification and lead optimization. This review will focus on cutting-edge technologies used in most recent studies on the design of PPAR- γ agonists and will discuss the chemistry of a few molecules which emerged successful. Virtual screening of natural product libraries is an effective strategy to harness nature as the source of ligands for PPARs. Databases of natural products, drug molecules, and chemical substances facilitate this approach, where these molecules are virtually screened by similarity search, ADMETox properties, pharmacophore modelling and shape-based modelling. Docking is a valuable in-silico approach to probe the PPAR-ligand interaction. Rigid docking of ligands with various crystallized structures of the PPARs is a routinely used model. Induced fit docking and core hopping approach in docking were reported as rapid screening methods to identify novel leads and to predict the PPAR- γ and PPAR-α/ γ dual agonistic activity. One-dimensional drug profile matching is one of the recent virtual screening methods by which an antiprotozoal drug, Nitazoxanide, was identified as a PPAR- γ agonist. Virtual screening workflow can be customized by choosing appropriate models and applying them either sequentially or simultaneously to achieve convincing and reliable results.
Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is ... more Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, β-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the a...
UV-spectrophotometric determination of dissociation constant (pKa) is used routinely in various r... more UV-spectrophotometric determination of dissociation constant (pKa) is used routinely in various research fields. This review highlights the structural attributes of organic compounds that exhibit distinct pH-sensitive UV-absorbance for ionized and unionized species qualifying for pKa measurement. Organic compounds must possess a double bond, the chromophore adjacent to the ionizing functional group. Compounds bearing up to five sigma bonds between the chromophore and ionizing group are eligible for UV-spectrophotometric determination of pKa. This review serves as a quick guide for knowledge about structural requirements expediting pKa determination by UV-spectrophotometry. Besides, the study also identified the gap in research on pKa in drug discovery and food chemistry, revealing the necessity of determining pKa at the early stages of drug and food research to enhance the success rate in their development.
International Journal of Medicinal Chemistry, 2017
Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. ... more Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogue...
Watercress oil (WCO) is the seed oil of Nasturtium officinale, Brassicaceae family. WCO is a cosm... more Watercress oil (WCO) is the seed oil of Nasturtium officinale, Brassicaceae family. WCO is a cosmetic for hair growth approved by the Saudi Food and Drug Authority (SFDA). The study aimed to analyze by GC–MS, the phytochemical profile and the safety of WCO as a cosmetic according to SFDA, validates the traditional method of applying hot oil mixtures to the scalp, and also reports the pH, UV absorption, and in-silico binding mechanism of fatty acids for hair growth. The absorption of UV-B light (284.50 nm and 290.60 nm) by WCO suggests that it acts as a sunscreen for the scalp. The pH of the marketed WCO, 5.53 ± 0.02, shall not damage the scalp and hair. The GC–MS analysis confirmed fatty acids as the principal constituents (65.65%) of WCO composed of monounsaturated fatty acids (MUFAs): cis-11-Octadecenoic acid (17.14%), cis-9-Octadecenoic acid (17.11%), cis-13-Eicosenoic acid (11.13%), cis-11-Eicosenoic acid (3.48%), and cis-13-Docosenoic acid (1.64%); saturated fatty acid: n-Hexad...
Purpose: To develop a high performance thin-layer chromatography (HPTLC procedure for quantitatio... more Purpose: To develop a high performance thin-layer chromatography (HPTLC procedure for quantitation of apigenin in ethanol extract of Matricaria chamomilla (Babunaj) flowers, and to evaluate the extract for in vitro cytotoxic effect on MCF-7 cell lines. Methods: Quantification of apigenin was carried out using a CAMAG TLC system. A combination of toluene, ethyl acetate and formic acid (4.5:3.5:0.2 v/v/v) was used as mobile phase, with densitometry detection at 336 nm. The HPTLC procedure was subjected to validation as per ICH guidelines. The cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: A sharp apigenin band at Rf of 0.51 was obtained, and the content of apigenin in the extract was 0.062 % w/w. The detection limit (LOD) and quantification limit (LOQ) were 0.19 and 0.57 ng/band, respectively. MTT assay results indicate that M. chamomilla was cytotoxic to Michigan Cancer Foundation-7 (MCF-7) cells, with h...
Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric k... more Polymeric lipid hybrid nanoparticles (PLNs) are core–shell nanoparticles made up of a polymeric kernel and lipid/lipid–PEG shells that have the physical stability and biocompatibility of both polymeric nanoparticles and liposomes. PLNs have emerged as a highly potent and promising nanocarrier for a variety of biomedical uses, including drug delivery and biomedical imaging, owing to recent developments in nanomedicine. In contrast with other forms of drug delivery systems, PLNs have been regarded as seamless and stable because they are simple to prepare and exhibit excellent stability. Natural, semi-synthetic, and synthetic polymers have been used to make these nanocarriers. Due to their small scale, PLNs can be used in a number of applications, including anticancer therapy, gene delivery, vaccine delivery, and bioimaging. These nanoparticles are also self-assembled in a reproducible and predictable manner using a single or two-step nanoprecipitation process, making them significantl...
Computational assessment of the binding interactions of drugs is an important component of comput... more Computational assessment of the binding interactions of drugs is an important component of computer-aided drug design paradigms. In this perspective, a set of 30 1-(substituted phenyl)-3-(naphtha[1, 2-d] thiazol-2-yl) urea/thiourea derivatives showing antiparkinsonian activity were docked into inhibitor binding cavity of human adenosine A2A receptor (AA2AR) to understand their mode of binding interactions in silico. Lamarckian genetic algorithm methodology was employed for docking simulations using AutoDock 4.2 program. The results signify that the molecular docking approach is reliable and produces a good correlation coefficient (r2 = 0.483) between docking score and antiparkinsonian activity (in terms of % reduction in catalepsy score). Potent antiparkinsonian agents carried methoxy group in the phenyl ring, exhibited both hydrophilic and lipophilic interactions with lower energy of binding at the AA2AR. These molecular docking analyses should, in our view, contribute for further ...
Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified p... more Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide...
Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial a... more Background and Objectives: Drug design strategies to develop novel broad-spectrum antibacterial agents for the treatment of respiratory tract infections that can combat bacterial resistance are currently gaining momentum. 2,4- thiazolidinedione is a structural scaffold that contains pharmacophores similar to β-lactam and non- β-lactam antibiotics. The objective of the study was to synthesize newer 3,5-disubstituted-2,4-thiazolidinediones (DTZDs) and subject them to in-vitro antibacterial screening against bacterial pathogens. Also, we performed in-silico docking of selected compounds to penicillin-binding proteins and beta-lactamases. Methods: Intermediate Schiff bases were prepared by reaction between 2,4-thiazolidinedione and an appropriate aldehyde followed by acylation of the ring nitrogen with 3-brompropanoyl chloride resulting in DTZDs. Minimum inhibitory concentrations were determined against few bacteria infecting the respiratory tract by the broth tube dilution method. Zone...
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Papers by Neelaveni Thangavel