Molecules

The computational method for estimating the geometry of two coupled hydrogen bonds with geometries close to linear using a pair of spectral NMR parameters was proposed. The method was developed based on the quantum-chemical investigation of 61 complexes with two hydrogen bonds formed by oxygen and nitrogen atoms of the 4-hydroxypyridine anion with OH groups of substituted methanols. The main idea of the method is as follows: from the NMR chemical shifts of nuclei of atoms forming the 4-hydroxylpyridine anion, we select such pairs, whose values can be used for simultaneous determination of the geometry of two hydrogen bonds, despite the fact that every NMR parameter is sensitive to the geometry of each of the hydrogen bonds. For these parameters, two-dimensional maps of dependencies of NMR chemical shifts on interatomic distances in two hydrogen bonds were constructed. It is shown that, in addition to chemical shifts of the nitrogen atom and quaternary carbon, which are experimentally difficult to obtain, chemical shifts of the carbons and protons of the CH groups can be used. The performance of the proposed method was evaluated computationally as well on three additional complexes with substituted alcohols. It was found that, for all considered cases, hydrogen bond geometries estimated using two-dimensional correlations differed from those directly calculated by quantum-chemical methods by not more than 0.04 Å. Full article

Oxyresveratrol (OXY) has been reported for its anti-inflammatory activity; however, the pharmaceutical applications of this compound are limited by its physicochemical properties and poor pharmacokinetic profiles. The use of an ester prodrug is a promising strategy to overcome these obstacles. In previous researches, several carboxylate esters of OXY were synthesized and oxyresveratrol tetraacetate (OXY-TAc) was reported to possess anti-melanogenic and anti-skin-aging properties. In this study, in addition to OXY-TAc, two novel ester prodrugs of OXY, oxyresveratrol tetrapropionate (OXY-TPr), and oxyresveratrol tetrabutyrate (OXY-TBu), were synthesized. Results from the Caco-2-permeation assay suggested that synthesized ester prodrugs can improve the membrane-permeation ability of OXY. The OXY-TAc exhibited the most significant profile, then this prodrug was chosen to observe anti-inflammatory activities with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results showed that OXY-Tac significantly alleviated secretion of several pro-inflammatory mediators (nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), mitigated expression of enzyme-regulated inflammation (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and suppressed the MAPK cascades. Interestingly, the observed anti-inflammatory activities of OXY-TAc were more remarkable than those of its parent compound OXY. Taken together, we demonstrated that OXY-TAc improved physicochemical and pharmacokinetic profiles and enhanced the pharmacological effects of OXY. Hence, the results in the present study would strongly support the clinical utilities of OXY-TAc for the treatment of inflammation-related disorders. Full article

Houttuynia cordata is a medicinal and edible plant with a wide biological interest. Many parts were discarded due to various modes of consumption, resulting in resource waste. In this study, a comprehensive study was conducted on various edible indicators and medicinal components of Houttuynia cordata to understand its edible and medicinal value. The edible indexes of each root, stem, and leaf were determined, and the metabolites of different parts were investigated using the headspace solid-phase micro-extraction technique (HS-SPME-GC-MS). The differential metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS-DA) and clustering analysis. The results of the study showed that the parts of Houttuynia cordata with high edibility values as a vegetable were mainly the roots and leaves, with the highest vitamin C content in the roots and the highest total flavonoids, soluble sugars, and total protein in the leaves. The nutrient content of all the stems of Houttuynia cordata was lower and significantly different from the roots and leaves (p < 0.05). In addition, 209 metabolites were isolated from Houttuynia cordata, 135 in the roots, 146 in the stems, 158 in the leaves, and 91 shared metabolites. The clustering analysis and OPLS-DA found that the parts of Houttuynia cordata can be mainly divided into above-ground parts (leaves and stems) and underground parts (roots). When comparing the differential metabolites between the above-ground parts and underground parts, it was found that the most important medicinal component of Houttuynia cordata, 2-undecanone, was mainly concentrated in the underground parts. The cluster analysis resulted in 28 metabolites with up-regulation and 17 metabolites with down-regulation in the underground parts. Most of the main components of the underground part have pharmacological effects such as anti-inflammatory, anti-bacterial and antiviral, which are more suitable for drug development. Furthermore, the above-ground part has more spice components and good antioxidant capacity, which is suitable for the extraction of edible flavors. Therefore, by comparing and analyzing the differences between the edible and medicinal uses of different parts of Houttuynia cordata as a medicinal and food plant, good insights can be obtained into food development, pharmaceutical applications, agricultural development, and the hygiene and cosmetic industries. This paper provides a scientific basis for quality control and clinical use. Full article

In the context of the increasing lactation problems among breastfeeding women, the development of a healthy lifestyle is needed. Different variants of pork, turkey, and beef meatballs, with added lemon balm (Melissa officinalis L.) and wild thyme (Thymus serpyllum L.) aqueous extract (6%), were obtained. These herbs were selected and used due to their antioxidant, antimicrobial, and lactogenic potential. Two thermal treatments, hot air convection (180 °C) and steam convection (94 °C), were applied for meatballs processing. The obtained meatballs were further subjected to a complex characterization. The functionality of the plant extracts was proved by the values of total content of polyphenols (2.69 ± 0.02 mg AG/g dw) and flavonoids (3.03 ± 0.24 mg EQ/g dw). FT-IR analysis confirmed the presence of trans-anethole and estragole at 1507–1508 cm⁻¹ and 1635–1638 cm⁻¹, respectively. Costumers’ overall acceptance had a score above 5.5 for all samples, on a scale of 1 to 9. Further analysis and human trials should be considered regarding the use of lactogenic herbs, given their health benefits and availability. Full article

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans. Full article

Cyclic pentaphenylalanine was studied as an efficient anion sensor for halides, thiocyanate and oxoanions in acetonitrile and methanol. Stability constants of the corresponding complexes were determined by means of fluorimetric, spectrophotometric, ¹H NMR, and microcalorimetric titrations. A detailed structural overview of receptor–anion complexes was obtained by classical molecular dynamics (MD) simulations. The results of ¹H NMR and MD studies indicated that the bound anions were coordinated by the amide groups of cyclopeptide, as expected. Circular dichroism (CD) titrations were also carried out in acetonitrile. To the best of our knowledge, this is the first example of the detection of anion binding by cyclopeptide using CD spectroscopy. The CD spectra were calculated from the structures obtained by MD simulations and were qualitatively in agreement with the experimental data. The stoichiometry of almost all complexes was 1:1 (receptor:anion), except for dihydrogen phosphate where the binding of dihydrogen phosphate dimer was observed in acetonitrile. The affinity of the cyclopeptide receptor was correlated with the structure of anion coordination sphere, as well as with the solvation properties of the examined solvents. Full article

Peptides are promising molecular-binding elements and have attracted great interest in novel biosensor development. In this study, a series of peptides derived from odorant-binding proteins (OBPs) were rationally designed for recognition of SARS-CoV-2-related volatile organic compounds (VOCs). Ethanol, nonanal, benzaldehyde, acetic acid, and acetone were selected as representative VOCs in the exhaled breath during the COVID-19 infection. Computational docking and prediction tools were utilized for OBPs peptide characterization and analysis. Multiple parameters, including the docking model, binding affinity, sequence specification, and structural folding, were investigated. The results demonstrated a rational, rapid, and efficient approach for designing breath-borne VOC-recognition peptides, which could further improve the biosensor performance for pioneering COVID-19 screening and many other applications. Full article

Juice made from sea-buckthorn berries (Hippophae rhamnoides L.) is a valuable source of bioactive compounds, vitamins, as well as micro- and macronutrients. By applying defatted sea-buckthorn juice, it is possible to enhance wheat beer and change its sensory properties and the contents of bioactive compounds in the finished product. A sensory assessment showed that wheat beers with a 5% v/v addition of sea-buckthorn juice were characterised by a balanced taste and aroma (overall impression). Physicochemical analyses showed that, compared to the control samples, wheat beers enhanced with defatted sea-buckthorn juice at a rate of 5% v/v or 10% v/v had high total acidity with respective mean values of 5.30 and 6.88 (0.1 M NaOH/100 mL), energy values lower on average by 4.04% and 8.35%, respective polyphenol contents of 274.1 mg GAE/L and 249.7 mg GAE/L, as well as higher antioxidant activity (measured using DPPH, FRAP, and ABTS assays). The findings show that the samples of wheat beer enhanced with sea-buckthorn juice had average ascorbic acid contents of 2.5 and 4.5 mg/100 mL (in samples with 5% v/v and 10% v/v additions, respectively) and contained flavone glycosides, e.g., kaempferol-3-O-glucuronide-7-O-hexoside. Based on the current findings, it can be concluded that wheat beer enhanced with sea-buckthorn juice could emerge as a new trend in the brewing industry. Full article

Contaminants of emerging concern (CECs) are compounds of diverse origins that have not been deeply studied in the past which are now accruing growing environmental interest. The NOR-Water project aimed to identify the main CECs and their sources in the water environment of Northern Portugal–Galicia (located in northwest Spain) transnational region. To achieve these goals, a suspect screening analytical methodology based on the use of liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) was applied to 29 sampling sites in two campaigns. These sampling sites included river and sea water, as well as treated wastewater. The screening was driven by a library of over 3500 compounds, which included 604 compounds prioritized from different relevant lists on the basis of the persistency, mobility, and toxicity criteria. Thus, a total of 343 chemicals could be tentatively identified in the analyzed samples. This list of 343 identified chemicals was submitted to the classification workflow used for prioritization and resulted in 153 chemicals tentatively classified as persistent, mobile, and toxic (PMT) and 23 as very persistent and very mobile (vMvP), pinpointing the relevance of these types of chemicals in the aqueous environment. Pharmaceuticals, such as the antidepressant venlafaxine or the antipsychotic sulpiride, and industrial chemicals, especially high production volume chemicals (HPVC) such as ε-caprolactam, were the groups of compounds that were detected at the highest frequencies. Full article

Near-infrared (NIR) fluorescence materials have exhibited formidable power in the field of biomedicine, benefiting from their merits of low autofluorescence background, reduced photon scattering, and deeper penetration depth. Fluorophores possessing planar conformation may confront the shortcomings of aggregation-caused quenching effects at the aggregate level. Fortunately, the concept of aggregation-induced emission (AIE) thoroughly reverses this dilemma. AIE bioconjugates referring to the combination of luminogens showing an AIE nature with biomolecules possessing specific functionalities are generated via the covalent conjugation between AIEgens and functional biological species, covering carbohydrates, peptides, proteins, DNA, and so on. This perfect integration breeds unique superiorities containing high brightness, good water solubility, versatile functionalities, and prominent biosafety. In this review, we summarize the recent progresses of NIR-emissive AIE bioconjugates focusing on their design principles and biomedical applications. Furthermore, a brief prospect of the challenges and opportunities of AIE bioconjugates for a wide range of biomedical applications is presented. Full article

Advanced glycation end products (AGEs) are stable products produced by the reaction of macromolecules such as proteins, lipids or nucleic acids with glucose or other reducing monosaccharides, which can be identified by immunohistochemistry in the senile plaques and neurofibrillary tangles of Alzheimer’s disease (AD) patients. Growing evidence suggests that AGEs are important risk factors for the development and progression of AD. 1,8-cineole (CIN) is a monoterpenoid compound which exists in many plant essential oils and has been proven to have neuroprotective activity, but its specific effect and molecular mechanisms are not clear. In this study, AGEs-induced neuronal injury and intracerebroventricular-AGE animals as the possible models for AD were employed to investigate the effects of CIN on AD pathology as well as the molecular mechanisms involved both in vivo and in vitro. Our study demonstrated that CIN could ameliorate tau phosphorylation by down-regulating the activity of GSK-3β and reducing Aβ production by inhibiting the activity of BACE-1 both in vivo and in vitro. It is suggested that CIN has certain therapeutic value in the treatment of AD. Full article

Stinging nettle (Urtica dioica L.) is a common perennial herb well known for its therapeutic, cosmetic and food use. Despite the popularity of nettle hydrolate, there is currently no literature describing its composition; likewise, there is still a lack of research describing in detail the parameters of hydrolates in general. U. dioica hydrolate fractions were obtained by industrial steam distillation of fresh herb. Total stinging nettle hydrolate was prepared by mixing an equal volume of each fraction. The volatiles were isolated from hydrolate samples by liquid–liquid extraction with diethyl ether, and analysed using GC-FID-MS. Over eighty volatile compounds were identified in U. dioica hydrolate. The main group of constituents were oxygenated compounds, mainly alcohols (e.g., (E)- and (Z)-hex-3-en-1-ol, carvacrol) and oxides (e.g., caryophyllene oxide). The content of volatiles in the representative sample of total hydrolate amounted to 58.2 mg/L. Some qualitative and quantitative changes in the composition of U. dioica hydrolate were observed during the progress of distillation. The content of low chain aliphatic alcohols ((E)- and (Z)-hex-3-en-1-ol) decreased, whereas the percentage of some monoterpene alcohols (carvacrol and α-terpineol) increased. The total content of volatiles in hydrolate also changed and decreased (128.0–6.2 mg/L) during distillation progress. According to our results, to produce stinging nettle hydrolate of good quality, the proper relationship between the amount of hydrolate and raw plant material should result in obtaining 0.74 L hydrolate from 1 kg of fresh stinging nettle herb. Therefore, it may be assumed that the high alcohol content may increase the microbiological stability of the product. Full article

Acute myeloid leukemia (AML) accounts for approximately 15–20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML. Full article

Screening of a library of novel N-hydroxylactams amenable by the Castagnoli-Cushman reaction identified four lead compounds that facilitated ⁵⁵Fe transport into P. aeruginosa cells (one of these synthetic siderophores was found to be as efficient at promoting iron uptake as the natural siderophores pyoverdine, pyochelin or enterobactin). Conjugates of the four lead siderophores with ciprofloxacin were tested for antibacterial activity against P. aeruginosa POA1 (wild type) and the ∆pvdF∆pchA mutant strain. The antibacterial activity was found to be pronounced against the ∆pvdF∆pchA mutant strain grown in CAA medium but not for the POA1 strain. This may be indicative of these compounds being ‘Trojan horse’ antibiotics. Further scrutiny of the mechanism of the antibacterial action of the newly developed conjugates is warranted. Full article

Objectives Green tea (Camellia sinensis) is a kind of unfermented tea that retains the natural substance in fresh leaves to a great extent. It is regarded as the second most popular drink in the world besides water. In this paper, the phytochemistry, pharmacology, and toxicology of green tea are reviewed systematically and comprehensively. Key findings Green tea has been demonstrated to be good for human health. Nowadays, multiple pharmacologically active components have been isolated and identified from green tea, including tea polyphenols, alkaloids, amino acids, polysaccharides, and volatile components. Recent studies have demonstrated that green tea shows versatile pharmacological activities, such as antioxidant, anticancer, hypoglycemic, antibacterial, antiviral, and neuroprotective. Studies on the toxic effects of green tea extract and its main ingredients have also raised concerns including hepatotoxicity and DNA damage. Summary Green tea can be used to assist the treatment of diabetes, Alzheimer’s disease, oral cancer, and dermatitis. Consequently, green tea has shown promising practical prospects in health care and disease prevention. Full article

Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of licorice. Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 μm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin. Full article

Ferulasinkins A–D (1–4), four new norlignans, were isolated from the resins of Ferula sinkiangensis, a medicinal plant of the Apiaceae family. All of them were obtained as racemic mixtures, chiral HPLC was used to produce their (+)- and (−)-antipodes. The structures of these new compounds, including their absolute configurations, were elucidated by spectroscopic and computational methods. This isolation provides new insight into the chemical profiling of F. sinkiangensis resins beyond the well-investigated structure types such as sesquiterpene coumarins and disulfides. Compounds 2a and 3a were found to significantly inhibit the invasion and migration of triple-negative breast cancer (TNBC) cell lines via CCK-8 assay. On the other hand, the wound-healing assay also demonstrated that compounds 4a and 4b could promote the proliferation of human umbilical vein endothelial cells (HUVECs). Notably, the promoting effects of 4a and 4b were observed as more significant versus a positive control using basic fibroblast growth factor (bFGF). Full article

In this work, we designed and synthesized a novel series of quinazoline derivatives 6-19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC₅₀ value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC₅₀ = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future. Full article

In this study, the volatile compound profiles of gurum seed oil were determined using two methods: supercritical CO₂ extraction (SFE) and the screw press process (SPP). For volatile compounds extraction and identification, headspace solid-phase micro-extraction (HS-SPME) and GC–MS were used, respectively. A total number of 56 volatile compounds were revealed and identified in oil extracted by SFE, while only 40 compounds were detected in extracted oil by SPP. Acids, aldehydes, esters, ketones, furans, and other components were present in the highest ratio in oil extracted by SFE. In contrast, alcohols and alkenes were found in the highest proportion in oil extracted by SPP. In this study, it was observed that SFE showed an increase in the amounts of volatile compounds and favorably impacted the aroma of gurum seed oil. The results reveal that different extraction methods significantly impact the volatile components of gurum seed oil, and this study can help evaluate the quality of the oil extracted from gurum seeds. Full article