Search

Gut microbiota modulates host physiology and pathophysiology through the production of microbial metabolites. Diet is a crucial factor in shaping the microbiome, and gut microbes interact with the host by producing beneficial or detrimental diet-derived microbial metabolites. Evidence from our lab and others indicates that the interaction between diet and gut microbes plays a pivotal role in modulating vascular health. Diet-derived microbial metabolites such as short-chain fatty acids and metabolites of phenolic acids improve vascular health, whereas trimethylamine oxide and certain amino acid-derived microbial metabolites impair the vasculature. These metabolites have been shown to regulate blood pressure, vascular inflammation, and atherosclerosis by acting on multiple targets. Nonetheless, there are substantial gaps in knowledge within this field. The microbial enzymes essential for the production of diet-derived metabolites, the role of the food matrix in regulating the bioavailability of metabolites, and the structure-activity relationships between metabolites and biomolecules in the vasculature are largely unknown. Potential diet-derived metabolites to improve vascular health can be identified through future studies that investigate the causal relationship between dietary components, gut microbes, diet-derived metabolites, and vascular health by using radiolabeled compounds, metabolomics, transcriptomics, and proteomics techniques. [ABSTRACT FROM AUTHOR]

Natural products of plant origin are of high interest and widely used, especially in the food industry, due to their low toxicity and wide range of bioactive properties. Compared to other plant components, the safety of polysaccharides has been generally recognized. As dietary fibers, plant-derived polysaccharides are mostly degraded in the intestine by polysaccharide-degrading enzymes secreted by gut microbiota, and have potential prebiotic activity in both non-disease and disease states, which should not be overlooked, especially in terms of their involvement in the treatment of intestinal diseases and the promotion of intestinal health. This review elucidates the regulatory effects of plant-derived polysaccharides on gut microbiota and summarizes the mechanisms involved in targeting gut microbiota for the treatment of intestinal diseases. Further, the structure-activity relationships between different structural types of plant-derived polysaccharides and the occurrence of their prebiotic activity are further explored. Finally, the practical applications of plant-derived polysaccharides in food production and food packaging are summarized and discussed, providing important references for expanding the application of plant-derived polysaccharides in the food industry or developing functional dietary supplements. [ABSTRACT FROM AUTHOR]

Momordica charantia L. is a well-known medicine and food homology plant with high pharmaceutical and nutritional values. Polysaccharides are carbohydrate polymers connected by glycosidic bonds, one of the key functional ingredients of M. charantia. Recently, M. charantia polysaccharides (MCPs) have attracted much attention from industries and researchers due to their anti-oxidant, anti-tumor, anti-diabetes, anti-bacteria, immunomodulatory, neuroprotection, and organ protection activities. However, the development and utilization of MCPs-based functional foods and medicines were hindered by the lack of a deeper understanding of the structure-activity relationship (SAR), structural modification, applications, and safety of MCPs. Herein, we provide an overview of the extraction, purification, structural characterization, bioactivities, and mechanisms of MCPs. Besides, SAR, toxicities, application, and influences of the modification associated with bioactivities are spotlighted, and the potential development and future study direction are scrutinized. This review provides knowledge and research underpinnings for the further research and application of MCPs as therapeutic agents and functional food additives. [ABSTRACT FROM AUTHOR]

As a research hotspot in food science and nutrition, antioxidant peptides can function by scavenging free radicals, inhibiting peroxides, and chelating metal ions. Therefore, how to efficiently discover and screen antioxidant peptides has become a key issue in research and production. Traditional discovery methods are time-consuming and costly, but also challenging to resolve the quantitative structure-activity relationship of antioxidant peptides. Several novel techniques, including artificial intelligence, molecular docking, bioinformatics, quantum chemistry, phage display, switchSENSE, surface plasmon resonance, and fluorescence polarization, are emerging rapidly as solutions. These techniques possess efficient capability for the discovery of antioxidant peptides, even with the potential for high-throughput screening. In addition, the quantitative structure-activity relationship can be resolved. Notably, combining these novel techniques can overcome the drawbacks of a single one, thus improving efficiency and expanding the discovery horizon. This review has summarized eight novel and efficient techniques for discovering antioxidant peptides and the combination of techniques. This review aims to provide scientific evidence and perspectives for antioxidant peptide research. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Twelve new limonoids (1—12), named trichilitins A—L, were isolated from the leaves and twigs of Trichilia connaroides, together with ten known compounds (13—22). The structures were elucidated by extensive spectroscopic investigations, X‐ray diffraction analyses, and ECD calculations. Compound 1, which belongs to a unique class of ring B‐seco limonoid, has been identified as 6/7/6/5 tetracyclic due to a key Baeyer‐Villiger oxidation. Compounds 2—7 were identified as ring intact limonoids, while compounds 8—10 were established as ring D‐seco ones, and 11 and 12 were determined to be rearranged ones. All of the compounds were tested for cytotoxicity against three human tumor cell lines (HCT‐116, NCl‐H1975, and SH‐SY5Y). Compounds 6, 7, 13, 14, and 19 exhibited significant cytotoxic effects, especially 7 exhibited significant cytotoxic effects against HCT‐116 with an IC50 value of 0.035 μmol·L–1 and was more active than the positive control, doxorubicin with an IC50 value of 0.20 μmol·L–1. Compound 7 effectively induced apoptosis of HCT‐116, which was associated with S‐phase cell cycle arrest. Furthermore, the Western blot analysis showed that compound 7 could induce cell cycle arrest by promoting the expression levels of p53 and p21. [ABSTRACT FROM AUTHOR]

Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this study, eighteen triterpene squalene-derived polyethers, including twelve natural products and six synthetic derivatives, obtained from the red alga Laurencia viridis Gil-Rodríguez & Haroun were screened for their antiproliferative activity against six cancer cell lines: A549, HBL-100, HeLa, SW1573, T-47D, and WiDr; and a structure-activity relationship (SAR) study was established. [ABSTRACT FROM AUTHOR]

Scanning electrochemical microscopy (SECM) is a scanning probe technique capable of imaging substrate topography and measuring the local electrochemical reactivity of interfaces. Since introduced by Allen J. Bard and co-workers in 1989, it has expanded into a wide variety of fields, such as nanomaterial characterization, energy, kinetics, electrocatalysis, metal anti-corrosion, biology and instrumental development. SECM uses an ultra-microelectrode as the probe to record redox current during probe scanning across sample surfaces to obtain local topography and electrochemical reactivity of samples. Specifically, three main topics are reviewed and discussed: (1) the working principles and operating modes of SECM; (2) the recent developments in the application of SECM in energy science, including solar cell, rechargeable batteries, fuel cells and supercapacitors, with an emphasis on the last five years (2019–2023); (3) the perspectives and outlook of SECM in various energy devices. We anticipate that a wider adoption of SECM by the energy community will allow for the operando characterization of many types of reactions, and hold the potential to provide new insights into the structure/activity and composition/activity relationships. [ABSTRACT FROM AUTHOR]

Creating cost-effective and efficient electrocatalysts for the sluggish oxygen evolution reaction (OER) is crucial for practical implementation of hydrogen production via water electrolysis, advancing metal-air batteries, and converting CO2 into value-added chemicals. Transition metal hydroxides, particularly those containing iron (Fe), show promise as OER catalysts, yet the relationship between material properties and catalysis remains unclear. Recent advances in in-situ/operando approaches, notably 57Fe Mössbauer spectroscopy, enable real-time monitoring of catalysts and reveal structural characteristics of Fe species. This review highlights case studies involving in-situ/operando 57Fe Mössbauer techniques in Fe-involved metal hydroxide OER electrocatalysis, providing insights into Fe's role, active sites, and catalytic mechanisms. The investigation aims to assess opportunities and challenges linked to the use of in-situ/operando Mössbauer spectroscopy, shedding light on potential advancements in this critical research area. [ABSTRACT FROM AUTHOR]

The layered N-doped tungsten carbide (WC) with enhanced electrical conductivity was designed and fabricated via a facile molten-salt-chemistry-assisted strategy as electrocatalytic material for efficient hydrogen evolution reaction (HER), which is a prospective and feasible approach for green and carbon-neutral hydrogen energy storage. The layered WC structure was in situ formed via carbonization procedure utilizing the as-prepared WO 3 microspheres as substrates. The microstructure, physicochemical properties, and electrocatalytic HER performance of WC catalysts can be regulated by the treatment temperature ranging from 700 to 1000 °C during the molten-salt-chemistry-assisted processes with NaCl/KCl mixture as the molten salt. The engineered WC/C-900 catalyst with optimized components of W, C, and N elements, synergistic effect, and enhanced electrical conductivity provides high HER performance with an overpotential of 188 mV (684 mV of WO 3) and long-term 28 h stability at 10 mA cm−2 in acidic medium. Additionally, in-depth insights into the catalyst microstructure, temperature-dependent phase transition, surface/interface properties, structure-activity relationships, and HER mechanism of the versatile material on the basis of theoretical calculation and experimental discovery are also investigated. • The layered WC is fabricated by a facile molten-salt-chemistry-assisted strategy. • Carbonization temperatures can regulate physicochemical properties of WC catalysts. • WC/C-900 displays enhanced electrical conductivity and synergistic effect. • The WC/C-900 catalyst exhibits high HER performance and long-term stability. [ABSTRACT FROM AUTHOR]

Flavonoids have long been used as food additives due to their antioxidant properties. To discover bioactive natural flavonoids, the antioxidant capabilities of a range of natural flavonoids were investigated in RAW 264.7 cells and Caenorhabditis elegans induced by H2O2. Chemical antioxidant activity of a range of flavonoids was performed by DPPH and ABTS+ radicals scavenging assays. Then, the cellular antioxidant activity assays were employed to detect the antioxidant mechanisms by flow cytometry and qRT‐PCR analyses. The underlying antioxidant mechanisms were explored by western blotting, small interfering RNA (siRNA), molecular docking, and cellular thermal shift assay (CETSA). Next, the antioxidant potential of active compounds was verified in H2O2‐induced Caenorhabditis elegans. Our studies showed herbacetin exhibited the most pronounced DPPH and ABTS + radicals scavenging capacity among all the tested flavonoids. And herbacetin also showed improved antioxidant activity against H2O2‐induced oxidative stress in RAW 264.7 cells compared to quercetin and Trolox. The structure‐activity relationship (SAR) analysis indicated that hydroxyl groups at the 7′ and 8′ positions on the A‐ring of herbacetin played a crucial role in inhibiting H2O2‐induced cellular oxidative stress. Interestingly, herbacetin's activation of HO‐1 was closely associated with its binding to Keap1. Notably, in vivo assays demonstrated that herbacetin protected Caenorhabditis elegans from H2O2‐induced oxidative stress. This study screens and elucidates the excellent antioxidant capacity of herbacetin both in vitro and in vivo. These findings suggest that herbacetin holds promise as a natural agent for antioxidant therapy. [ABSTRACT FROM AUTHOR]

Deep ultraviolet (DUV) nonlinear optical (NLO) crystals with balanced performance are crucial for extending laser wavelengths into the DUV region, essential for various laser applications. However, developing ideal DUV crystals is challenging due to stringent requirements: strong second‐harmonic generation (SHG) response, short cut‐off wavelength, and effective phase‐matching behavior. DUV NLO borates, which feature π‐conjugated groups, have garnered attention for their higher SHG coefficients compared to phosphates. However, phosphates typically show short UV cut‐off edges due to the large HOMO‐LUMO gap (approximately 9.6 eV) of the [PO₄] units. To enhance the SHG effect while maintaining DUV transparency in phosphates, several strategies have been proposed: 1) using distorted polymerized P−O groups like isolated C₁‐[P₃O₁₀]⁵− and [P₂O₇]⁴−; 2) aligning isolated [PO₄]3− tetrahedra along the polar screw axis; 3) introducing additional NLO‐active units; and 4) exploring new units derived from [PO₄]3−, such as [PO₃F]2− tetrahedra. These strategies have led to the successful development of various non‐centrosymmetric phosphates, highlighting their potential as DUV NLO candidates. This review explores the relationship between their crystal structures and DUV NLO performance, and proposes future directions for developing ideal DUV NLO materials. [ABSTRACT FROM AUTHOR]

Background: Primary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity. This study aims to further examine the ability of the ddE-based approach in improving QSAR mutagenicity predictions for PAAs and to develop a refined method to decrease false positive predictions. Results: Information on 1,177 PAAs was collected, of which 420 were from public databases and 757 were from in-house databases across 16 laboratories. The total dataset included 465 Ames test-positive and 712 test-negative chemicals. For internal PAAs, detailed Ames test data were scrutinized and final decisions were made using common evaluation criteria. In this study, ddE calculations were performed using a convenient and consistent protocol. An optimal ddE cutoff value of -5 kcal/mol, combined with a molecular weight ≤ 500 and ortho substitution groups yielded well-balanced prediction scores: sensitivity of 72.0%, specificity of 75.9%, PPV of 65.6%, negative predictive value of 80.9% and a balanced accuracy of 74.0%. The PPV of the ddE-based approach was greatly reduced by the presence of two ortho substituent groups of ethyl or larger, as because almost all of them were negative in the Ames test regardless of their ddE values, probably due to steric hindrance affecting interactions between the PAA and metabolic enzymes. The great majority of the PAAs whose molecular weights were greater than 500 were also negative in Ames test, despite ddE predictions indicating positive mutagenicity. Conclusions: This study proposes a refined approach to enhance the accuracy of QSAR mutagenicity predictions for PAAs by minimizing false positives. This integrative approach incorporating molecular weight, ortho substitution patterns, and ddE values, substantially can provide a more reliable basis for evaluating the genotoxic potential of PAAs. [ABSTRACT FROM AUTHOR]

Rate coefficients, k(T), for the gas‐phase OH radical reaction with decamethyltetrasiloxane ((CH3)3SiO[Si(CH3)2O]2Si(CH3)3, L4, k1), dodecamethylpentasiloxane ((CH3)3SiO[Si(CH3)2O]3Si(CH3)3, L5, k2), and decamethylcyclopentasiloxane ([–Si(CH3)2O–]5, D5, k3), and dodecamethylcyclohexasiloxane ([–Si(CH3)2O–]6, D6, k4) were measured using a pulsed laser photolysis—laser induced fluorescence absolute method over the temperature range 270–370 K. The obtained room temperature rate coefficients, with quoted 2σ absolute uncertainties, and fitted temperature dependence are (cm−3 molecule−1 s−1): k1295K=2.50±0.18×10−12,k1270−370K=1.707×10−13T/2984.45exp807/Tk2295K=3.12±0.32×10−12,k2295−370K=2.65±0.02×10−11exp−630±60/Tk3295K=2.02±0.12×10−12,k3270−370K=8.97×10−13T/2982.90exp248/Tk4297K=2.89±0.16×10−12,k4297−370K=3.13±0.05×10−11exp−717±119/T$$\begin{equation*} \hspace*{45pt} \def\eqcellsep{&}\begin{array}{rcl} {k}_1\left( {295\;{\mathrm{K}}} \right) &=& \left( {2.50 \pm 0.18} \right) \times {{10}}^{ - 12},\quad {k}_1\left( {270-370\;{\mathrm{K}}} \right)\\ & =& 1.707 \times {{10}}^{ - 13}{{\left( {{\mathrm{T}}/298} \right)}}^{4.45}\exp \left( {807/{\mathrm{T}}} \right)\\ {k}_2\left( {295\;{\mathrm{K}}} \right) &=& \left( {3.12 \pm 0.32} \right) \times {{10}}^{ - 12},\quad {k}_2\left( {295-370\;{\mathrm{K}}} \right)\\ &=& \left( {2.65 \pm 0.02} \right) \times {{10}}^{ - 11}\exp \left( { - \left( {630 \pm 60} \right)/{\mathrm{T}}} \right)\\ {k}_3\left( {295\;{\mathrm{K}}} \right) &=& \left( {2.02 \pm 0.12} \right) \times {{10}}^{ - 12},\quad {k}_3\left( {270-370\;{\mathrm{K}}} \right)\\ & =& 8.97 \times {{10}}^{ - 13}{{\left( {T/298} \right)}}^{2.90}\exp \left( {248/{\mathrm{T}}} \right)\\ {k}_4\left( {297\;{\mathrm{K}}} \right) &=& \left( {2.89 \pm 0.16} \right) \times {{10}}^{ - 12},\quad {k}_4\left( {297-370\;{\mathrm{K}}} \right)\\ & =& \left( {3.13 \pm 0.05} \right) \times {{10}}^{ - 11}\exp \left( { - \left( {717 \pm 119} \right)/{\mathrm{T}}} \right) \end{array} \end{equation*}$$The 2σ absolute rate coefficient uncertainty, for all compounds included in this study, is conservatively estimated to be ∼10% over the entire temperature range. The cyclic permethylsiloxanes were found to be less reactive than the analogous linear compound, while both linear and cyclic compounds show increasing reactivity with increasing number of CH3‐ groups. A structure activity relationship (SAR) parameterization for the permethylsiloxanes is presented. The estimated atmospheric lifetimes due to OH reaction for L4, L5, D5, and D6 are 5.2, 4.4, 6.8, and 5.2 days, respectively. [ABSTRACT FROM AUTHOR]

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation. [Display omitted] • BPRMU191 exemplifies an antagonist-to-agonist modulator of mu-opioid receptor (MOR) • BPRMU191 converts opioid antagonists to G protein-biased agonists of MOR • BPRMU191 /opioid antagonist combination induces analgesia while minimizing side effects • Antagonist-to-agonist modulators of GPCRs display strong therapeutic potential Huang, Lin, and Ou et al. identified BPRMU191 , a small molecule that endows morphinan antagonists of mu-opioid receptor with agonistic properties, thereby activating the receptor and inducing analgesia. This work demonstrates an effective approach for modulating the activity of G protein-coupled receptors by small molecules that modulate the receptor conformation. [ABSTRACT FROM AUTHOR]

The Chemical Communications journal, published by The Royal Society of Chemistry, features articles on various topics such as ionomer performance, catalysis for plastic waste, and multiphase coacervates. The journal also covers research on DNA G-quadruplex targeting molecules, metal-organic cages, and sodium-ion batteries. Additionally, it includes studies on organic photonic heterostructures, spin crossover complexes, and electrochemical nitrate reduction. The articles provide insights into cutting-edge research in the field of chemistry. [Extracted from the article]

Selenium-polysaccharide (Se-polysaccharide) is an organic Se compound that binds polysaccharides to Se via unique chemical interactions. Se-polysaccharide, as a functional supplement, has minimal harmful effects and is more easily absorbed and utilized by the body. Currently, there are three techniques to obtain Se-polysaccharide. Numerous studies have demonstrated that selenization modification can alter the structural and physical characterization of polysaccharide. Furthermore, Se-polysaccharide possesses stronger biological attributes, including immunomodulation, antitumor, antioxidant, hypoglycaemic, heavy metal resistance, neuroprotection, anti-inflammatory, liver protection, and other aspects, than Se and polysaccharide. Scientific studies suggest that Se-polysaccharide has the potential for future development and show that it is an effective treatment for several diseases. This paper systematically introduces the preparation methods of Se-polysaccharide, discusses the impact of selenization modification on the structural and physical characterization of polysaccharide, and analyses the biological activities and potential mechanism of Se-polysaccharides in recent years. Additionally, further research directions are proposed and provided theoretical basis for development of Se-polysaccharide. [ABSTRACT FROM AUTHOR]

Anion exchange membrane fuel cells (AEMFCs) are advantageous for reducing or even eliminating the dependency on platinum resources, as the alkaline environment allows the use of non‐precious metal catalysts for oxygen reduction reaction at the cathode. However, the intrinsic activity of hydrogen oxidation reaction (HOR) catalysts in alkaline environments is 2 to 4 orders of magnitude lower than in acidic environments, which becomes the major challenge for AEMFCs. This review examines the current developments in the intrinsic activity of alkaline HOR catalysts and systematically summarizes the hydrogen activation mechanism with a focus on potential influencing factors and enhancement strategies. Furthermore, it offers insights into the prospects for developing more efficient alkaline HOR catalysts. [ABSTRACT FROM AUTHOR]

Providencia stuartii, the most prevalent strain in its genus, is a significant cause of a range of potentially fatal diseases involving urinary tract infections, lung diseases, and endocarditis, often exhibiting resistance to multiple antibiotics, necessitating alternative therapeutic approaches. Unlike previous efforts focused on known virulence factors, this study delves into the physicochemical and functional characterization of 72 essential hypothetical proteins (EsHPs) from the P. stuartii BE246 genome. Subcellular localization identified 47 cytoplasmic EsHPs as potential drug targets, with the remainder 25 identified as vaccine targets. Subtractive analysis uncovered 68 virulent proteins, 4 of which were nonhomologous to both host and gut microbiota proteomes. Among these, WP_145928235.1 (147 amino acids), a cytoplasmic EsHP, emerged as a novel drug target due to its homologous broad‐spectrum hit. WP_145928235.1 displayed an instability index (II) of 33.14, an aliphatic index of 92.79, and the GRAVY score was ‐0.065 (hydrophilic). Molecular dynamics simulation‐aided conformational study and secondary structure analysis highlighted the protein's flexibility and propensity to interact with inhibitors. Key residues in the 60–90 region, including Asn62, Gly75, Glu81, and Asp85, were critical for interactions and stability, with low frustration indicating residual conservancy. WP_145928235.1 presents a promising target for therapeutic intervention against multidrug‐resistant P. stuartii infections. [ABSTRACT FROM AUTHOR]

In our efforts to design mono‐carbonyl analogues of curcumin with potential antiplasmodial activity, diarylidenecyclopentanone (DACP) derivatives, Ia–Iu and II–V, have been synthesized and characterized using 1H NMR, 13C NMR, IR, UV–Vis, and mass spectrometry. Structure of one of these DACPs has been verified by single crystal XRD. At the outset, all 25 DACPs were first screened at 12.5 µM for their in vitro antiplasmodial activity against the chloroquine (CQ)‐sensitive Pf3D7. The three most potent compounds (In, It, and Ik) were further tested at <10 µM concentrations against Pf3D7, PfINDO (CQ resistant), and PfMRA‐1240 (Artemisinin resistant) strains for determination of their IC50s and resistance indices. The drug profile of the DACPs was found to be very promising, with the most active compound It (IC50 1.39 µM against PfINDO) showing a selectivity index of ∼17 tested using HUH‐7 and HEK‐293T mammalian cell lines. Molecular docking studies with Pf pyridoxal synthase showed a good correlation between docking scores of DACPs and in vitro antiplasmodial activity. Further, high conformity with Lipinski's parameters indicates that these DACPs are promising antiplasmodial lead compounds. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: TAG‐assisted peptide synthesis technology enables optimal conservation of Fmoc amino acid raw materials and chemical solvents while eliminating the need for intricate chromatographic purification processes. This work presents a 4,4'‐diphenylphosphonoxy diphenylcarbinol tag‐mediated liquid‐phase synthesis approach for preparing side‐to‐tail cyclopeptides macolacin which has strong activity against gram‐negative bacteria, and its 15 analogues containing four N‐methylation modified cyclopeptides, as well as an investigation of their structure‐activity relationship (SAR). The synthesis of macolacin analogues primarily focuses on the modifications of the N‐methylation group of Ile‐7 and the tail fatty acyl chain of macolacin. The incorporation of N‐methylation for Ile‐7, along with the dihalogenated or monohalogenated benzoic acids for tail modification, exhibited remarkable antibacterial efficacy and minimal hepatocellular toxicity in vitro. The present study identified an N‐methylation‐modified antimicrobial cyclopeptide Ma14 that exhibits rapid bactericidal efficacy against A. baumanii, etc., while showing reduced hepatocellular toxicity. Molecular docking simulations were conducted to investigate the binding of cyclopeptides to the outer membrane protein BamA of A. baumannii. The findings demonstrated the stable binding interactions of the cyclopeptides with the BamA protein and then presented a novel approach to explain the bacteriostatic mechanism of macolacin‐based cyclopeptide antibiotics. [ABSTRACT FROM AUTHOR]

A series of 6 novel ester derivatives 2–7 of natural product geodin 1 were designed and semi-synthesized through one mild step reaction with high yield. Compounds 2–7 showed strong inhibitory activities against Staphylococcus aureus in the range of 2.35–9.41 μM. Compounds 4 and 7 showed very strong inhibitory activities against antifouling bacteria Aeromonas salmonicida with MICs of 2.42 μM and 4.56 μM respectively. Most notably compounds 3–7 showed potent antifungal activities against Candida albicans in the range of 0.59–2.44 μM. Particularly, compound 3 showed the highest antifungal activity against C. albicans with a MIC value of 0.59 μM. The preliminary structure activity relationship of these derivatives showed that replacement of 4-OH group with benzoyl substituents could enhance the antibacterial and antifungal activities of geodin 1. [ABSTRACT FROM AUTHOR]

In this work, the rapid and efficient preparation of isolated galloyl glucoside tautomer free radical inhibitors was investigated using Saxifraga tangutica as a raw material. Four highly polar galloyl glucoside tautomers, 3-O-galloyl-α-d-glucose ⇌ 3-O-galloyl-β-d-glucose (Fr2-1-1), 2-O-galloyl-α-d-glucose ⇌ 2-O-galloyl-β-d-glucose (Fr2-1-2/2-1-3), 1-O-galloyl-β-d-glucose (Fr2-2-1), and 6-O-galloyl-α-d-glucose ⇌ 6-O-galloyl-β-d-glucose (Fr2-3-1/Fr2-3-2), were obtained via two-step medium-pressure liquid chromatography (with solid loading instead of conventional liquid injection) and one-step high-performance chromatography coupled with on-line RPLC-DPPH techniques for targeted isolation. This separation integration technique not only increases sample intake and reduces time cost but also visualizes each step of targeted separation. All four compounds were isolated from the plant for the first time. In vitro antioxidant activity assays by DPPH (1,1‑diphenyl-2-picrylhydrazyl) revealed that Fr2-1-2/Fr2-1-3 (IC50: 5.52 ± 0.32 μM), Fr2-2-1 (IC50: 7.22 ± 0.57 μM), and Fr2-3–1/Fr2-3-2 (IC50: 7.36 ± 0.25 μM) had superior free radical scavenging abilities and that both were superior to that of quercetin (IC50: 18.61 ± 3.55 μM). Oxidative stress assays revealed that Fr2-1-2/Fr2-1-3 significantly inhibited oxidative stress damage in H2O2-induced HepG2 cells, decreased the level of ROS (P < 0.01) and protected hepatocytes. Combined with the current results, gallic acid showed greater antioxidant activity when H atoms were replaced at d-glucose –OH (C-2) than at the other three sites [–OH (C-1), –OH (C-6) and –OH (C-3)]. [ABSTRACT FROM AUTHOR]

Natural products, with their extensive chemical diversity, distinctive biological activities, and vast reservoirs, provide a robust foundation for advancing cancer therapeutics. A comprehensive phytochemical investigation of the skins from Bufo bufo gargarizans afforded two new bufadienolide derivatives identified as bufalactamides A and B (1–2), along with six known compounds: argentinogenin (3), desacetylcinobufagin (4), desacetylcinobufaginol (5), cinobufaginol (6), bufalin (7) and gamabufalin (8). The structural elucidation of these compounds was meticulously carried out by analyses of spectroscopic data (1D and 2D NMR, HR-ESIMS), and comparison with the literature data. Plausible biosynthetic pathways for the new compounds were also discussed. Moreover, the cytotoxicity of the compounds was investigated using various cancer cell lines, including lung cancer (A549), colon cancer (HCT-116), liver cancer (SK-Hep-1), and ovarian cancer (SKOV3). Our research findings indicated that compounds 3, and 6–8 exhibit potent cytotoxic activity (IC50 < 2.5 µM). In contrast, compounds 4 and 5 display moderate cytotoxic activity (IC50 < 50 µM) while compounds 1 and 2 show no cytotoxic activity (IC50 > 100 µM). From this data, we conducted a comprehensive analysis of the structure-activity relationships among these compounds. [ABSTRACT FROM AUTHOR]

Homorepeats are motifs with reiterations of the same amino acid. They are prevalent in proteins associated with diverse physiological functions but also linked to several pathologies. Structural characterization of homorepeats has remained largely elusive, primarily because they generally occur in the disordered regions or proteins. Here, we address this subject by combining structures derived from machine learning with conformational sampling through physics-based simulations. We find that hydrophobic homorepeats have a tendency to fold into structured secondary conformations, while hydrophilic ones predominantly exist in unstructured states. Our data show that the flexibility rendered by disorder is a critical component besides the chemical feature that drives homorepeats composition toward hydrophilicity. The formation of regular secondary structures also influences their solubility, as pathologically relevant homorepeats display a direct correlation between repeat expansion, induction of helicity, and self-assembly. Our study provides critical insights into the conformational landscape of protein homorepeats and their structure-activity relationship. [Display omitted] • Insights into homorepeat structures by integrating AlphaFold with MD simulations • Homorepeats of different amino acids exhibit significant conformational diversity • Intrinsic disorder promotes the hydrophilic compositional bias of homorepeats • Homorepeat length expansion induces disorder-to-order transition and aggregation Bonet et al. have combined AlphaFold, a state-of-the-art protein structure prediction method, with molecular dynamics simulations to show that homorepeats can fold into diverse conformational states. Their study provides fundamental insights into the structural features of this under-characterized motifs, with potential implications for understanding their biological activity in proteins. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure–activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure–activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments. [ABSTRACT FROM AUTHOR]

Ceria (CeO2) is a widely used oxide catalyst, yet the nature of its active sites remains elusive. This study combines model and powder catalyst studies to elucidate the structure-activity relationships in ceria-catalyzed CO activation and hydrogenation. Well-defined ceria clusters are synthesized on planar CeO2(111) and exhibit dynamic and tunable ranges of Ce coordination numbers, which enhance their interaction with CO. Reduced ceria clusters (e.g., Ce3O3) bind CO strongly and facilitate its dissociation, while near-stoichiometric clusters (e.g., Ce3O7) adsorb CO weakly and promote oxidation via carbonate formation. Unlike planar ceria surfaces, supported ceria clusters exhibit dynamic properties and enhanced catalytic activity, that mimic those of powder ceria catalysts. Insight from model studies provide a method to quantify active sites on powder ceria and guide further optimization of ceria catalysts for syngas conversion. This work marks a leap toward model-guided catalyst design and highlights the importance of site-specific catalysis. This study combines model and powder catalyst studies to elucidate the atomic-scale structure-reactivity relationships in ceria-catalyzed CO hydrogenation, optimizing ceria catalysts for syngas conversion and advancing model-guided catalyst design. [ABSTRACT FROM AUTHOR]

Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. The cystobactamids, discovered from myxobacterial sources, have a unique hexapeptidic scaffold with five arylamides and possess potent, resistance-breaking properties. This study investigates the role of the central D-ring pharmacophore in cystobactamids, a para-aminobenzoic acid (PABA) moiety that is additionally substituted by hydroxy and isopropoxy functions. We varied the two oxygenated substituents and replaced both amide connectors with bioisosteres. Synthetic routes were developed that included metal-mediated aromatic functionalization or heterocycle formations, leading to 19 novel analogues. The antibiotic efficacy of all analogues was determined against bacteria from the ESKAPE pathogen panel. While the replacement and the repositioning of hydroxy and isopropoxy substituents was not advantageous, exchanging PABA by terephthalic acid amides led to the highly potent analogue 42 with broad-spectrum activity, insensitivity towards AlbD-mediated degradation and promising pharmacokinetic properties in mice. The study highlights the steep structure-activity relationships in the tetrasubstituted D-ring and a surprisingly favorable reversion of the amide connecting C and D. Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. Here, the authors assess the role of the central D ring pharmacophore in cystobactamids, and develop a potent broad-spectrum antibiotic by exchanging a para-aminobenzoic acid with a terephthalic acid amide. [ABSTRACT FROM AUTHOR]

Muscular dystrophies encompass a heterogeneous group of rare neuromuscular diseases characterized by progressive muscle degeneration and weakness. Among these, Duchenne muscular dystrophy (DMD) stands out as one of the most severe forms. The present study employs an integrative approach combining network pharmacology, quantitative structure-activity relationship (QSAR) modeling, molecular dynamics (MD) simulations, and free energy calculations to identify potential therapeutic targets and natural compounds for DMD. Upon analyzing the GSE38417 dataset, it was found that individuals with DMD exhibited 290 upregulated differentially expressed genes (DEGs) compared to healthy controls. By utilizing gene ontology (GO) and protein-protein interaction (PPI) network analysis, this study provides insights into the functional roles of the identified DEGs, identifying ten hub genes that play a critical role in the pathology of DMD. These key genes include DMD, TTN, PLEC, DTNA, PKP2, SLC24A, FBXO32, SNTA1, SMAD3, and NOS1. Furthermore, through the use of ligand-based pharmacophore modeling and virtual screening, three natural compounds were identified as potential inhibitors. Among these, compounds 3874518 and 12314417 have demonstrated significant promise as an inhibitor of the SMAD3 protein, a crucial factor in the fibrotic and inflammatory mechanisms associated with DMD. The therapeutic potential of the compounds was further supported by molecular dynamics simulation and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis. These findings suggest that the compounds are viable candidates for experimental validation against DMD. [ABSTRACT FROM AUTHOR]

Background/Objectives: Current promising treatments for many diseases are based on the use of therapeutic nucleic acids, including DNA. However, the list of nanocarriers is limited due to their low biocompatibility, high cost, and toxicity. The design of synthetic building blocks for creating universal delivery systems for genetic material is an unsolved problem. In this work, we propose PAMAM dendrimers with rigid thiacalixarene core in various conformations, i.e., PAMAM-calix-dendrimers, as a platform for a supramolecular universal constructor for nanomedicine. Results: Third generation PAMAM dendrimers with a macrocyclic core in three conformations (cone, partial cone, and 1,3-alternate) were synthesized for the first time. The obtained dendrimers were capable of binding and compacting calf thymus DNA, whereby the binding efficiency improved with increasing generation, while the influence of the macrocyclic core was reduced. A dramatic effect of the macrocyclic core conformation on the hemolytic activity of PAMAM-calix-dendrimers was observed. Specifically, a notable reduction in hemotoxicity was associated with a decrease in compound amphiphilicity. Conclusions: We hope the results will help reduce financial and labor costs in developing new drug delivery systems based on dendrimers. [ABSTRACT FROM AUTHOR]

The present study describes an eco‐friendly NBS‐assisted regioselective synthesis of new 5‐acylfunctionalized 5‐acylfunctionalized 2‐(1H‐pyrazol‐1‐yl)thiazoles by condensation of 3,5‐dimethyl‐1H‐pyrazole‐1‐carbothioamide with unsymmetrical 1,3‐diketones under solvent‐free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a–j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 μg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 μg/mL and 62.5 μg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 μg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100μg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed. [ABSTRACT FROM AUTHOR]

Context: This study addresses the development of sustainable pyridinium ionic liquids (ILs) because of their potential applications in agriculture and pharmaceuticals. Pyridinium-based ILs are known for their low melting points, high thermal stability, and moderate solvation properties. We synthesized three novel pyridinium-based ILs: 1-(2-(isopentyloxy)-2-oxoethyl)pyridin-1-ium chloride, 1-(2-(hexyloxy)-2-oxoethyl)pyridin-1-ium chloride, and 1-(2-(benzyloxy)-2-oxoethyl)pyridin-1-ium chloride. The biological activities of these compounds were evaluated through plant growth promotion, herbicidal, and insecticidal assays. Our results show that the benzyloxy derivative significantly enhances wheat and cucumber growth, whereas the isopentyloxy compound has potent herbicidal effects. Computational methods, including DFT calculations and molecular docking, were applied to understand the structure‒activity relationships (SARs) and mechanisms of action. Methods: The computational techniques involved dispersion-corrected density functional theory (DFT) with the B3LYP functional and the 6-311G** basis set. Grimme's D3 corrections were included to account for dispersion interactions. The calculations were performed via GAMESS-US software. Quantum descriptors of reactivity, such as ionization potential, electron affinity, chemical potential, and electrophilicity index, were derived from the HOMO and LUMO energies. Molecular docking studies were conducted via the CB-Dock server via AutoDock Vina software to predict binding affinities to cancer-related proteins. Petra/Osiris/Molinspiration (POM) analysis was used to predict the drug likeness and other pharmaceutical properties of the synthesized ILs. [ABSTRACT FROM AUTHOR]

Vanilloid analogs, which can activate transient receptor potential vanilloid 1 (TRPV1), have been classified into two types based on susceptibility to forskolin (FSK). Treatment of cells expressing TRPV1 with FSK enhances TRPV1 responses to capsaicin-type ligands while diminishing the responses to eugenol-type ligands. In this study, we determined the effect of FSK on the activation of TRPV1 stimulated with vanilloid ligands, through the influx of Ca2+ in HEK293T cells expressing TRPV1. Our findings suggest that the effects of FSK can be attributed to the phosphorylation of TRPV1, as evidenced by using a protein kinase A inhibitor and TRPV1 mutants at potential phosphorylation sites. Furthermore, we examined the structure-activity relationship of 13 vanilloid analogs. Our results indicated that vanilloid compounds could be classified into three types, that is the previously reported two types and a novel type of 10-shogaol, by which TRPV1 activation was insusceptible to the FSK treatment. [ABSTRACT FROM AUTHOR]

Paw swelling induced by carrageenan injection serves as a reliable model for assessing acute inflammatory responses in rats. In this study, we synthesized and evaluated a series of quinoxaline derivatives for their anti-inflammatory activity using the carrageenan-induced rat hind paw edema method. The compounds 5a, 5e, 5f, 5g, 5h, 5l, 5q, and 5u were selected based on their inhibitory activity against p38a MAP kinase. Among these, compound 5f, which possesses a 2-chlorophenyl group at position 4 of the triazole ring, demonstrated the highest inhibition of paw edema, with an 84.15% reduction, comparable to the standard drug diclofenac sodium (83.22%). The structure-activity relationship revealed that the presence of a chloro group at the 6th position of the quinoxaline ring led to reduced anti-inflammatory activity. This study highlights the potential of quinoxaline derivatives as effective anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Noble-metal-free CO2 reduction systems based on cobalt phthalocyanine (CoPc) and its derivatives have demonstrated remarkable photocatalytic performances; however, their structure-activity relationship with electronic tuning remains unexplored. Herein, we now provide a systematic study to investigate the electron effects of substituents on the CoPc family in photocatalytic CO2 reduction, where a Cu(I) heteroleptic photosensitizer is utilized. The highest performance can be achieved using cobalt tetracarboxylphthalocyanine in light-driven CO2-to-CO reduction, with a maximum turnover number of 2950 at 450 nm and an outstanding apparent quantum yield of 63.5% at 425 nm, over ten times the activity with the tetra-dimethylamino-substituted CoPc derivative. The favorable electron-withdrawing effects have been further verified by DFT calculations and cyclic voltammetry, which reduces the overpotential required for CO2 reduction and decreases the Gibbs free energy of the catalyst active intermediates, particularly the CO-desorption energetics. [ABSTRACT FROM AUTHOR]

The controlled synthesis of precise carbon nanostructures with high electron conductivity, high reaction activity, and structural stability plays a significant role in practical applications yet largely unmet. Metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and coordination polymers (CPs) as crystalline porous materials (CPMs) have shown extraordinary porosity, tremendous structural diversity, and highly ordered pores, offering a platform for precise controlled carbon materials (CMs) with regular porous structures and high performances. Some recent studies have shown that CMs derived from CPMs with high specific surface area, superior chemical stability, excellent electrical conductivity offer a great opportunity for electrochemical energy storage and conversion. In this review, we summarize recent milestones of CPMs derived CMs in the field of capacitive energy storage. We hope the more precise design and control at the atomic level of CPMs could provide us a constructive view of the structure-activity relationship between CMs and electrochemical capacitors, as well as future trends and prospects. [ABSTRACT FROM AUTHOR]

Presently, there is a gap in the knowledge of the structure-activity relationship of immunomodulatory peptides. In this study, PFPEVFG was selected as a peptide with immunomodulatory activity from casein hydrolysate by virtual screening, and its immunomodulatory activity was verified by the phagocytosis, proliferation, and expression of cytokines (IL-6, IL-1β, TNF-α) and chemokines (CXCL1, CXCL2) in RAW 264.7 macrophages. Next, molecular docking and double-stranded small interfering RNA mutually verified that the immunomodulatory activity of PFPEVFG was mediated by TLR2 and TLR4. Furthermore, the highest occupied molecular orbital (HOMO) analysis showed that the C 19 =O 20 site with a HOMO contribution of 32.22988% was its active site, and the phenylalanine, where the C 19 =O 20 site was located, was its active amino acid. Finally, the combination of pathway inhibitors and western blot revealed that PFPEVFG activated macrophages through the nuclear factor-κB signaling pathway. In summary, this study provided a new perspective on deeply understanding the structure-activity relationship of casein-derived immunomodulatory peptides, as well as a further theoretical and technological basis for the application of immunomodulatory peptides. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Acanthopanax senticosus belongs to Araliaceae family and is traditionally used as a tonic. The roots and stems are mainly used as treatments for hypodynamia, rheumatism, and hypertension, but their frequent use may lead to extinction. However, comprehensive and simultaneous analysis of the remaining parts were still limited. There is a need to reorganize them for standardization of functional foods. In this study, 50 phenolic compounds and 82 triterpenoid saponins from the shoots, leaves, fruits, and stems of were characterized using UPLC-QTOF-MS and UPLC-QTRAP-MS/MS. Among them, 52 compounds were newly determined as the cis and malonyl-bound phenolic acids and were found to be structural isomers of Acanthopanax flavonoids and saponins. All compounds were absolutely/relatively quantified, and shoots had the highest content. Peroxynitrite and α-glucosidase inhibitory activities were performed, followed by evaluation of structure-activity relationships. Particularly, hederasaponin B and ciwujianoside B showed remarkable efficacy, which were affected by the C-23 hydroxylation, the C-20(29) double bond, and the presence of rhamnose. These detailed profiling can be used as fundamental data for increasing the utilization of A. senticosus and developing them into functional foods. [ABSTRACT FROM AUTHOR]

In view of the extremely important biological and medicinal properties of napthofurans, the synthesis of these heterocycles has fascinated the interest of medicinal and organic chemists. Keeping this in mind, we herein report the synthesis and antimicrobial evaluation of 4-N-aryl-naphtho[2,1-b]furo[3,2-d] pyrimidines 5 (a–l). Structures of these synthesized compounds were confirmed by spectral analysis like IR, NMR, and Mass spectrometry. The in vitro antimicrobial activities were reported for all the compounds 5 (a–l). The compounds 5e and 5f exhibited excellent antibacterial, antifungal, and antidermatophytic activities against tested pathogens at MIC 3.125, and 3.125 µg/mL, respectively. Furthermore, molecular docking studies of these compounds against S. aureus tyrosyl-tRNA synthetase (PDB ID: 1JIJ), S. aureus Gyrase (PDB ID: 2XCT), and SARS-CoV-2 Omicron (PDB ID: 7TOB), revealed the potential binding mode of the ligands to the site of the appropriate targets. Finally, drug-likeness and structure-activity relationship studies were also disclosed. [ABSTRACT FROM AUTHOR]

Quantitative Structure Activity Relationship (QSAR) requires the use of chemical descriptors which are either empirical or non-empirical. Although the ease of computation of computationally derived parameters such as given by ChemDraw software like CAA, CMA, CSEV and Dragon parameters like Au, Nc, Vs, TIC3, ATS2p etc. are easier to be used in the QSAR studies, but they still lack the biological interpretation as no prior knowledge of their physicochemical significance and their interrelationship is available. Therefore, the QSAR models developed using such parameters may be useful only in prediction of activity but are meaningless in terms of understanding the mode of action of the bioactive molecules. Thus, to fulfil this knowledge gap, and in continuation of our earlier work on physicochemical significance of topological parameters this study has been attempted to understand the empiricism of such computationally derived parameters in terms of their physicochemical significance. Here, we report that most of the ChemDraw and Dragon computed parameters are also best correlated with MR similar to topological parameters. [ABSTRACT FROM AUTHOR]

PLK4(polo-like kinase 4), an enzyme regulating centrioles, has been identified as a highly promising target for cancer treatment, making the development of PLK4 inhibitors crucial for advancing cancer therapy. In this study, 26 PLK4 inhibitors based on the imidazo[3,4- d ]pyrimidine scaffold, exhibiting anti-tumor activity, were selected. Reliable 3D/2D-QSAR models, Topomer CoMFA (q 2 =0.618, r 2 =0.965), and HQSAR (q 2 =0.711, r 2 =0.862), were established, demonstrating excellent internal and external predictive abilities and reliable applicability domains. Using the 3D/2D-QSAR models, nine PLK4 inhibitors with high theoretical activity were designed, and subsequent molecular docking and molecular dynamics studies revealed strong interactions between the new compounds and the receptor protein, particularly hydrophobic interactions. This research provides a robust screening model for the development of PLK4 inhibitors, offering valuable insights into the design of potential solutions to clinical challenges associated with PLK4 inhibitors. • Establishment of Reliable QSAR Models: Established excellent QSAR models to provide an in-depth elucidation of the structure-activity relationship of PLK4 inhibitors. • Molecular Docking and Molecular Dynamic Simulation: The study used molecular docking and molecular dynamics simulations to explore the microscopic binding mechanisms and stability between the newly designed inhibitors and the PLK4 receptor protein. • Design of Novel Inhibitors: Utilizing the QSAR models' predictive power, nine novel PLK4 inhibitors with high theoretical activity were designed, paving the way for new anti-cancer agents. • Contribution to Cancer Treatment: The design of these new PLK4-targeted inhibitors plays a significant role in cancer therapy, providing a targeted approach to treatment that may reduce off-target effects and the likelihood of drug resistance, underscoring the importance of computational technology in rational anti-cancer drug design. [ABSTRACT FROM AUTHOR]

Per‐ and polyfluoroalkyl substances (PFAS) are a class of chemicals present in a wide range of commercial and consumer products due to their water‐repellency, nonstick, or surfactant properties, resulting from their chemical and thermal stability. This stability, however, often leads to persistence in the environment when they are inevitability released. We utilized microbial microcosms from wastewater treatment plant (WWTP) sludge to determine how employing different functional groups such as heteroatom linkages, varying chain lengths, and hydrofluoroethers (HFEs) will impact the ultimate fate of these novel PFAS structures. A suite of five novel fluorosurfactant building blocks (F7C3OCHFCF2SCH2CH2OH (FESOH), F3COCHFCF2SCH2CH2OH (MeFESOH), F7C3OCHFCF2OCH2CH2OH (ProFdiEOH), F7C3OCHFCF2CH2OH (ProFEOH), and F3COCHFCF2OCH2CH2OH (MeFdiEOH)) and their select transformation products, were incubated in WWTP aerobic microcosms to determine structure–activity relationships. The HFE alcohol congeners with a thioether (FESOH and MeFESOH) were observed to transform faster than the ether congeners, while also producing second‐generation HFE acid products (F7C3OCHFC(O)OH (2H‐3:2 polyfluoroalkyl ether carboxylic acid [PFECA]) and F3COCHFC(O)OH (2H‐1:2 PFECA). Subsequent biodegradation experiments with 2H‐1:2 PFESA and 2H‐1:2 PFECA displayed no further transformation over 74 days. Surface water Photofate experiments compared 2H‐1:2 PFECA, and 2H‐1:2 polyfluorinated ether sulfonate (PFESA) with their fully fluorinated ether acid counterparts, and demonstrated the potential for both HFE acid species to completely mineralize over extended periods of time, a fate that highlights the value of studying novel PFAS functionalization. Environ Toxicol Chem 2024;43:2297–2305. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Polysaccharide is an important natural active ingredient, which has many biological activities such as antioxidation, antitumor and immunomodulation. And it has been widely used in biomedicine and health food. However, the huge molecular weight, complex spatial structure and vague structure-activity relationship of polysaccharide greatly limit the development and utilization of polysaccharide resources. Degradation can achieve structural modification and improve biological activity by reducing molecular weight and affecting its physicochemical properties and spatial conformation. Therefore, degradation may be an effective strategy to produce polysaccharides with excellent biological activity and analyze their structure-activity relationship. In this paper, the degradation methods of polysaccharides and the effects of degradation on their physicochemical properties and biological activities were reviewed. In addition, the development and application of polysaccharide degradation research and the existing problems were summarized and analyzed. This paper provided theoretical basis for polysaccharide degradation, development and utilization and structure-activity relationship research. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel carbon nitride catalysts prepared with cost-effective, low-temperature methods. • The materials show enhanced properties, higher surface areas and abundant basic sites. • Their catalytic activity is superior to conventional carbon nitride. • Threefold increase in CO 2 cycloaddition efficiency and stable catalytic activity. • This advancement has potential for converting CO 2 into valuable chemicals. The interest in using carbon nitrides (CN) for CO 2 conversion has stimulated extensive research on CN synthesis. Herein, we report the synthesis of two novel CN materials using low-cost commercially available precursors at low temperatures in a short duration of time. Two CN materials, one derived from 5-amino tetrazole (named 4NZ-CN) and the other derived from 3, 5-diamino-1, 2, 4-triazole (named 3NZ-CN) precursors, are prepared by refluxing these precursors for 2 h at 100 °C. 4NZ-CN and 3NZ-CN catalysts show higher surface areas (55.80 and 52.00 m2 g-1) and more basic sites (10.05 and 5.65 mmol g−1) than the conventional graphitic carbon nitride (g-C 3 N 4) derived from melamine, for which the corresponding values are 9.20 m2 g-1 and 0.62 mmol g−1, respectively. In addition, both CN exhibit a 3-fold higher catalytic activity for CO 2 cycloaddition to epoxides than g-C 3 N 4. The structure−activity relationship was ascertained using a combination of experimental and computational studies, and a catalytic mechanism was proposed. This work provides a facile strategy for the synthesis of novel CN materials at relatively low temperatures, and the developed catalysts show remarkable performance in the conversion of CO 2 to value-added chemicals. [ABSTRACT FROM AUTHOR]

In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines 16, 17, 18, and 22, as well as two unusual amine-linked bis-pleuromutilin examples 20 and 23, displayed variable levels of activity towards Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus, but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (30, 31) that exhibited activity towards both S. aureus ATCC 25923 and Escherichia coli ATCC 25922 with MIC 6.1–13.4 µM. Spermine–pleuromutilin analogue 31 was also able to enhance the action of doxycycline towards Pseudomonas aeruginosa ATCC 27853 by eight-fold, highlighting it as a useful scaffold for the development of new antibacterial pleuromutilin analogues that exhibit a broader spectrum of activity. [ABSTRACT FROM AUTHOR]

B-cell lymphoma 2 protein (Bcl-2) is an important regulator of cell apoptosis. Inhibitors that mirror the structural domain 3 (BH3) of Bcl-2 can activate apoptosis in cancer cells, making them a promising target for anticancer treatment. Hence, the present study aimed to investigate potential BH3-mimetic peptides from two vicilin-derived legume proteins from soybean and cowpea bean. The proteins were isolated and sequentially hydrolyzed with pepsin/pancreatin. Peptides < 3 kDa from vicilin-derived proteins from soybean and cowpea beans experimentally inhibited the growth of cultivated breast and prostate cancer cells. In silico analysis allowed the identification of six potential candidates, all predicted to be able to interact with the BH3 domain. The VIPAAY peptide from the soybean β-conglycinin β subunit showed the highest potential to interact with Bcl-2, comparable to Venetoclax, a well-known anticancer drug. Further experiments are needed to confirm this study's findings. [ABSTRACT FROM AUTHOR]

Carbohydrate digestive enzymes like α-amylase and α-glucosidase can be used to treat and manage diabetes. By inhibiting these enzymes, carbohydrate digestion slowed down, lowering the level of glucose entry into the bloodstream and preventing postprandial hyperglycemia. However, the effectiveness of current antidiabetic agents is limited due to their adverse effects. Therefore, the current study explored natural inhibitors from the methanol extract of rice to combat this issue. Through an integrated approach, four different rice cultivars were analysed and found that red rice methanol extract compounds stigmasterol and 1,2-benzenedicarboxylic acid interacted with α-amylase and α-glucosidase. Additionally, further research on stigmasterol directs the structure-activity relationship studies that aid in managing diabetic conditions. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, the new coronavirus variant, has been a worldwide health crisis that may outbreak at any time in the future. Over spans of human history, preparations derived from natural products have always been recognized as a preliminary source of medications. Taking into account the SARS-CoV-2 main protease (Mpro) as the essential element of the viral cycle and as a main target, herein we highlight a computer-aided comprehensive virtual screening for a focused chemical list of 14 laulimalides marine macrolides against SARS-CoV-2 Mpro using a set of integrated modern computational techniques including molecular docking (MDock), molecule dynamic simulations (MDS) and structure–activity relationships (SARs). Based on their remarkable ligand-protein energy scores and relevant binding affinities with SARS-CoV-2 (Mpro) pocket residues, two promising macrolides [laulimalides LA4 (6) and LA18 (13)] are selected as proposed inhibitor compounds. Consequently, they are thermodynamically investigated by deciphering their MD simulations at 100 ns, where they show noticeable stability within the accommodated (Mpro) pockets. Moreover, in-depth SARs studies suggest crucial roles for C-23 substituted side chain and C-20 methoxy as essential pharmacophoric structural features for activity. Further in vitro/vivo examinations of the selected marine macrolides would pave the way towards developing effective antiviral drugs from natural resources. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggested that polyphenols exhibited significant anti-hyperuricemia properties. However, multiple studies indicated that processing technologies caused the loss of polyphenols in plant materials, thereby reducing their bioactivities. Herein, studies on the beneficial effects of processing technologies on the anti-hyperuricemia effect of polyphenols were collected. Furthermore, the mechanisms of processing technologies promoted the anti-hyperuricemia effect of polyphenols were explored. Structure-activity relationships analysis showed that hydroxyl groups and C2=C3 double bond of polyphenols were beneficial for their anti-hyperuricemia activity. Conversely, glycosylation was a disadvantage to the anti-hyperuricemia activity of polyphenols. Moreover, improving the anti-hyperuricemia ability of polyphenols through appropriate processing technologies is a promising approach. Thermal treatment promoted the chemical conversion of polyphenols and increased the effective polyphenol content. Fermentation and enzymatic treatment promoted the bioconversion of polyphenols. Ultrasound regulated the conversion of polyphenols by impacting the polyphenol oxidase activity and affecting the dissolution rate and state of polyphenols. Encapsulation enhanced the bioavailability, stability, and solubility of polyphenols. Thus, the possible ways for processing technologies to enhance the anti-hyperuricemia effect of plant polyphenols were as follows: (1) Increasing the effective polyphenol content; (2) Promoting the beneficial chemical and biological conversion of polyphenols; (3) Enhancing the bioavailability, stability, and solubility of polyphenols. [ABSTRACT FROM AUTHOR]

The sodium-coupled neutral amino acid transporter SNAT2 (SLC38A2) has been shown to have important physiological functions and is implicated in various diseases like cancer. However, few compounds targeting this transporter have been identified and little is known about the structural requirements for SNAT2 binding. In this study, the aim was to establish the basic structure-activity relationship for SNAT2 using amino acid analogs. These analogs were first studied for their ability to inhibit SNAT2-mediated 3H-glycine uptake in hyperosmotically treated PC-3 cells. Then to identify substrates a FLIPR membrane potential assay and o-phthalaldehyde derivatization of intracellular amino with subsequent quantification using HPLC-Fl was used. The results showed that ester derivatives of the C-terminus maintained SNAT2 affinity, suggesting that the negative charge was less important. On the other hand, the positive charge at the N-terminus of the substrate and the ability to donate at least two hydrogen bonds to the binding site appeared important for SNAT2 recognition of the amine. Side chain charged amino acids generally had no affinity for SNAT2, but their non-charged derivatives were able to inhibit SNAT2-mediated 3H-glycine uptake, while also showing that amino acids of a notable length still had affinity for SNAT2. Several amino acid analogs appeared to be novel substrates of SNAT2, while γ-benzyl L-glutamate seemed to be inefficiently translocated by SNAT2. Elaborating on this structure could lead to the discovery of non-translocated inhibitors of SNAT2. Thus, the present study provides valuable insights into the basic structural binding requirements for SNAT2 and can aid the future discovery of compounds that target SNAT2. [ABSTRACT FROM AUTHOR]

Spread of antimicrobial resistances urges a need for new drugs against Mycobacterium tuberculosis (Mtb) with mechanisms differing from current antibiotics. Previously, callyaerins were identified as promising anti-tubercular agents, representing a class of hydrophobic cyclopeptides with an unusual (Z)-2,3-di-aminoacrylamide unit. Here, we investigated the molecular mechanisms underlying their antimycobacterial properties. Structure-activity relationship studies enabled the identification of structural determinants relevant for antibacterial activity. Callyaerins are bacteriostatics selectively active against Mtb, including extensively drug-resistant strains, with minimal cytotoxicity against human cells and promising intracellular activity. By combining mutant screens and various chemical proteomics approaches, we showed that callyaerins target the non-essential, Mtb-specific membrane protein Rv2113, triggering a complex dysregulation of the proteome, characterized by global downregulation of lipid biosynthesis, cell division, DNA repair, and replication. Our study thus identifies Rv2113 as a previously undescribed Mtb-specific drug target and demonstrates that also non-essential proteins may represent efficacious targets for antimycobacterial drugs. [Display omitted] • Flexible synthesis of callyaerin-type natural product analogs is developed • Callyaerins inhibit axenic and intracellular growth of Mycobacterium tuberculosis • Callyaerins target the non-essential membrane protein Rv2113 • Binding of callyaerins to Rv2113 causes a broad dysregulation of the proteome Podlesainski et al. develop natural and non-natural callyaerin derivatives that potently inhibit axenic and intracellular growth of Mycobacterium tuberculosis through establishing flexible synthesis of these derivatives. Chemoproteomics and mode-of-action studies identify the non-essential membrane protein Rv2113 as the target of callyaerins, which cause a broad dysregulation of the proteome. [ABSTRACT FROM AUTHOR]