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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]

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]

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]

Multivariate metal-organic frameworks (MTV-MOFs) are characterized by their unique structural feature of incorporating multiple organic linkers and metal ions into a unified framework. This composite construction bestows MTV-MOFs with a broader spectrum of diverse and intricate properties compared to traditional single-component MOFs. In this study, the performance of 560 MTV-MOFs as hydrogen storage adsorbents has been thoroughly investigated. Firstly, the key structural parameters of materials, including density, pore occupied accessible volume, accessible surface area, and porosity were computed. Then, high-throughput Grand Canonical Monte Carlo (GCMC) simulations were employed to calculate hydrogen adsorption capacity of MTV-MOFs under hydrogen pressures of 100 bar at both 77 K and 298 K. Based on simulated results, the deliverable hydrogen capacity of these MTV-MOFs were deduced under both room temperature conditions (298 K, 97.2 bar → 298 K, 5 bar) and low-temperature conditions (77 K, 100 bar → 160 K, 5 bar). Through high-throughput screening, we identified top ten promising MTV-MOFs with the highest hydrogen storage capacity and conducted in-depth studies on their hydrogen adsorption properties. Furthermore, we developed a multivariate linear regression model to quantitatively predict the relationship between hydrogen adsorption capacity and their structural parameters for these MTV-MOFs. The predictions of this model align closely with the outcomes derived from GCMC simulations. The present study highlights the potential of MTV-MOFs as promising candidates for hydrogen storage applications, thereby providing valuable theoretical insights into the exploration of high-capacity hydrogen storage materials. • Structural parameters and H 2 adsorption properties of 560 MTV-MOFs are studied. • Structure-activity relationships are systematically studied by statistical analysis. • The top ten MTV-MOFs with the best H 2 storage performance are identified. • Machine learning method is used to develop a multivariate linear regression model. [ABSTRACT FROM AUTHOR]

New graphene-nickel gallate nanocomplex (G-M-Ni) was designed, synthesized and characterized to deal with the requirement of functional combustion catalyst based on investigations of combustion mechanisms of propellant, structural analysis of catalyst and simulation results of quantum mechanics. The positive effect of G-M-Ni is not only reflected in the significantly increased burning rate, but also reflected in the reduction of friction sensitivity of composite modified double base (CMDB) propellant. The G-M-Ni nanocomplex exhibited significantly enhanced catalytic performances, and the burning rate of propellant at 20 MPa enhanced from 23.15 to 29.07 mm·s−1. Besides, the friction sensitivity of propellant reduced from 64 % to 36 % after addition of 0.5% G-M-Ni. The positive effect of G-M-Ni on CMDB propellant combustion is mainly attributed to its promotion impact on nitroglycerin (NG) pyrolysis, which significantly increased the differential charge density and decreased the decomposition activation energy (from 1.89 eV to 1.38 eV). The gas products produced by the rapid pyrolysis of NG are conducive to the heat feedback between the gas phase and the combustion surface, which makes the propellant have higher burning rate, bright flame, thin dark zone and flocculated quenching surface morphology. The findings in this study confirm the potential of G-M-Ni as a functional combustion catalyst for CMDB propellants, which has guiding significance and inspiration for the development of new combustion catalysts from the view of molecular-level insights. Recently, graphene based functional combustion catalysts have attracted much attention in the field of solid propellants due to their excellent catalytic combustion performance, reduced sensitivity, and improved mechanical properties. Herein, novel graphene-nickel gallate nanocomplex (G-M-Ni) were designed, synthesized and characterized to deal with the to deal with the requirement of functional combustion catalyst based on investigations of combustion mechanisms of CMDB propellant, structural analysis of new material and simulation results of quantum mechanics. By taking graphene as the benchmark, the G-M-Ni nanocomplex exhibited significantly enhanced catalytic performances, and excellent effect on the reduction of friction sensitivity. The relationship between molecular structure of G-M-Ni and combustion characteristics of CMDB propellant were disclosed. The theory-driven design mode of this work may provide new pathways to tune combustion behaviors of CMDB propellants from the view of molecular-level insights. The relationship between molecular structure of G-M-Ni and combustion characteristics of CMDB propellant were disclosed from the view of molecular-level insights. [Display omitted] • Graphene-nickel gallate nanocomplex (G-M-Ni) was first investigated in CMDB propellant. • G-M-Ni is conducive to the combustion and safety performance of CMDB propellant. • Explored the structure-activity relationship of G-M-Ni at the molecular level. • The key catalytic step of catalyst for CMDB propellant combustion was suggested. [ABSTRACT FROM AUTHOR]

Sulfonyl fluoride has attracted much attention due to its activatable reactivity, excellent biocompatibility and reactivity to proteins. In addition, sulfonyl fluoride has stronger spatial sensitivity and temporal sensitivity and can be used to study the localization and function of proteins. In a recent publication, a series of newly designed arylethenesulfonyl fluoride derivatives have emerged as highly effective inhibitors against methicillin-resistant Staphylococcus aureus (MRSA), showing impressive antiviral activity and antibiofilm properties. In order to gain a deeper understanding of the relationship between the structure and activity, this study used computational simulation methods such as 3D-QSAR, molecular docking and dynamics analysis to systematically study the structure–activity relationship of a series of arylethenesulfonyl fluoride compounds. Two different reliable 3D-QSAR statistical models, CoMFA (q2 = 0.668, SEE = 0.164, r2 = 0.962, F = 178.682) and CoMSIA/SEH (q2 = 0.6, SEE = 0.237, r2 = 0.916, F = 130.460), were established using a data set of 82 compounds. Analysis of three-dimensional contour maps revealed key structural features influencing molecular activity. Molecular docking studies examined the interaction modes between small molecules and the target protein SarA, identifying crucial residues such as LYS123. Based on the results and comparison of model prediction, we constructed 8 new molecules with better inhibitory activity than the template compounds. Molecular dynamics simulations verified the stable binding of the new molecules to the protein complex. The binding free energy results calculated by MM/PBSA are consistent with the activity prediction. Pharmacokinetic evaluation showed that the new molecule has good potential for clinical application. The new molecules studied here will provide the necessary theoretical basis for the synthesis and activity evaluation of new MRSA inhibitors. [ABSTRACT FROM AUTHOR]

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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 proteinprotein 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]

In this project, para‐carboxamidostilbene derivatives were synthesized using the Heck coupling reaction, confirmed through various analytical techniques such as FT‐IR, HRMS, and NMR analyses, and tested in vitro to evaluate their α‐amylase inhibitory activity. In silico molecular docking was employed to model the binding interactions of compounds with α‐amylase. Pharmacokinetic properties (ADME) and drug‐likeness were also examined. Structure activity relationship (SAR) analysis was conducted to establish the relationship between the chemical structure and α‐amylase inhibitory activity. The synthesized compounds exhibited significant α‐amylase inhibitory activity with IC50 values ranging from 15.0 to 37.5 µM in comparison with acarbose (IC50 = 30.2 ± 1.9 µM). Among them, compounds 6d–6f and 7c–7f demonstrated promising inhibitory activity. Furthermore, molecular docking studies revealed strong interactions between the studied molecules and the α‐amylase binding pocket. The drug‐likeness prediction results indicated that all synthesized compounds adhered to Lipinski's rule of five, suggesting their suitability as drug‐like molecules. Additionally, the assessment of ADMET properties indicated favorable absorption profiles, particularly in terms of human intestinal absorption (HIA). Overall, this study successfully identified several para‐carboxamidostilbene derivatives as potential α‐amylase inhibitors for the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Atomically dispersed metal atoms on supports exhibit distinctive advantages in maximizing atomic utilization, which plays an indispensable role in the fabrication of cost‐effective catalysts. In particular, dual‐atom catalysts (DACs) containing dual active sites not only retain the merits of single‐atom catalysts (SACs), but also introduce diverse interactions between the two adjacent metal atoms, endowing them with superior catalytic performance and a broad range of applications. With the development of DACs, it is important to identify active sites and establish intrinsic catalytic mechanisms relationship. The general characterization methods for DACs are comprehensively summarized here, especially the structural nature of dual active sites is discussed in detail. Subsequently, the representative scientific research efforts in various applications including thermocatalysis, electrocatalysis, and photocatalysis are described, with emphasis on structure‐property relationships. Finally, a summary and some prospects for the future of advanced DACs are presented. [ABSTRACT FROM AUTHOR]

The molecular basis of sweet taste toward various amino acids has not been fully elucidated. In this study, by correlation of their sweetness intensities with molecular properties, it is revealed that hydrophobic or dispersion force between side chains and sweet taste receptor (Tas1R2/Tas1R3) plays a prominent role for eliciting sweetness. Furthermore, the interaction modes of 13 amino acids with receptor indicate that amino (AH) and carboxyl (B) glucophores of different amino acids interact with identical residues of receptor, while the hydrophobic side chains (X glucophores) conduct distinct topological orientations with receptor, determining their chirality selection and sweetness intensities. Molecular dynamics analysis shows that sweet d‐amino acids move toward the hydrophobic transmembrane domain during activation with more contact numbers with receptor than nonsweet l‐amino acids, providing a mechanistic elucidation of previous inconsistent sensory evaluation results of specific amino acids. Moreover, by comparison with the interactions of a dipeptide sweetener, aspartame with Tas1R2/Tas1R3 and nonsweet l‐glutamate with class C G protein‐coupled receptors, we conclude that a complementary interaction mode with both hydrophilic and hydrophobic contacts accounts for the molecular origin of their sweet taste, presenting in‐depth insights and valuable guidelines for further molecular designs or modifications of amino acids‐derived sweeteners. [ABSTRACT FROM AUTHOR]

The negative implications for weeds encourage the finding of novel sources of phytotoxic agents for sustainable management. While traditional herbicides are effective, especially at large scales, the environmental impact and proliferation of resistant biotypes present major challenges that natural sources could mitigate. In this study, the potential of ginger metabolites as phytotoxic agents has been investigated for the first time. Root extracts, prepared via various extraction techniques, showed phytotoxicity in wheat (Triticum aestivum L. cv. Burgos) coleoptile bioassays at 800–100 ppm, and the most active extract (prepared by sonication with ethyl acetate) was purified by chromatographic methods, yielding seven compounds: five phenolic metabolites with gingerol and shogaol structures, β-sitosterol, and linoleic acid. Some of the major phenolic metabolites, especially [6]-shogaol and [6]-gingerol, exerted phytotoxicity on wheat coleoptiles, Plantago lanceolata and Portulaca oleracea (broadleaf dicotyledon weeds). This promoted the study of a collection of derivatives, revealing that the 5-methoxy, oxime, and acetylated derivatives of [6]-shogaol and [6]-gingerol had interesting phytotoxicities, providing clues for improving the stability of the isolated structures. Ginger roots have been demonstrated to be a promising source of bioactive metabolites for weed control, offering novel materials with potential for the development of agrochemicals based on natural products. [ABSTRACT FROM AUTHOR]

Compared with fossil-dependent process, glycerol hydrogenolysis to 1,2-propanediol (1,2-PDO) is a green sustainable route with much advantage. The commercial scale of this reaction has been achieved, and catalysts with high efficiency are continuously developed. Cu-based catalysts are considered as the most selective catalysts for 1,2-PDO production, which are widely investigated up to now. Understanding the structure-activity relationship can help the design of new catalytic materials with improved activity, selectivity and stability. In this review, the roles of various active structures on Cu catalysts are summarized. We introduce firstly the pioneering works, showing that Cu species are the primary active sites which can catalyze both the glycerol dehydration and C = O bond hydrogenation steps. Then, we summarize various viewpoints about the structure-sensitive effect of Cu in the reaction. The functions of support and promoter are subsequently discussed in detail, and the roles of the secondary metal site are further overviewed. After that, we propose critical factors that should be considered when investigating the Cu structure sensitive effect, and summarize three general roles of support, promoter and secondary metal. Further important research directions for Cu catalysts in glycerol hydrogenolysis are also outlined. [ABSTRACT FROM AUTHOR]

Natural products play a key role in drug discovery, both as a direct source of drugs and as a starting point for the development of synthetic compounds. Most natural products are not suitable to be used as drugs without further modification due to insufficient activity or poor pharmacokinetic properties. Choosing what modifications to make requires an understanding of the compound's structure--activity relationships. Use of structure--activity relationships is commonplace and essential in medicinal chemistry campaigns applied to human-designed synthetic compounds. Structure--activity relationships have also been used to improve the properties of natural products, but several challenges still limit these efforts. Here, we review methods for studying the structure--activity relationships of natural products and their limitations. Specifically, we will discuss how synthesis, including total synthesis, late-stage derivatization, chemoenzymatic synthetic pathways, and engineering and genome mining of biosynthetic pathways can be used to produce natural product analogs and discuss the challenges of each of these approaches. Finally, we will discuss computational methods including machine learning methods for analyzing the relationship between biosynthetic genes and product activity, computer aided drug design techniques, and interpretable artificial intelligence approaches towards elucidating structure--activity relationships from models trained to predict bioactivity from chemical structure. Our focus will be on these latter topics as their applications for natural products have not been extensively reviewed. We suggest that these methods are all complementary to each other, and that only collaborative efforts using a combination of these techniques will result in a full understanding of the structure--activity relationships of natural products. [ABSTRACT FROM AUTHOR]

Plants secrete defense resins rich in small-molecule natural products under abiotic and biotic stresses. This comprehensive review encompasses the literature published up to mid-2023 on medicinal plant resin natural products from six main contributor genera, featuring 275 citations that refer to 1115 structurally diverse compounds. The scope of this review extends to include essential information such as the racemic nature of metabolites found in different species of plant resins, source of resins, and revised structures. Additionally, we carefully analyze the reported biological activities of resins, organizing them based on the their structures. The findings offer important insights into the relationship between their structure and activity. Furthermore, this detailed examination can be valuable for researchers and scientists in the field of medicinal plant resin natural products and will promote continued exploration and progress in this area. [ABSTRACT FROM AUTHOR]

Covering mainly from 2013 up to 2023 with relevant references to work done before 2013 First reported in 1995, the dichapetalins and analogous compounds constitute a novel class of natural dammarane-type merotriterpenoids characterized by their unique 2-phenylpyrano moiety annellated to ring A of the dammarane skeleton. They have been reported from only two genera: Dichapetalum (Dichapetalaceae) and Phyllanthus (Phyllanthaceae). About 100 novel dichapetalins and dichapetalin-type compounds, including the acutissimatriterpenes and their antitumour and other bioactivities have been reported. In the present review, we cover the distribution, ethnobotanical and medicinal importance and the diversity of secondary metabolites reported from the two genera Dichapetalum and Phyllanthus from 2013 to date, with appropriate reference to relevant information prior to 2013. We also propose and discuss possible biosynthetic pathways, antitumour activity against a broad range of human and murine cancer cell lines, structure activity relationships, and other biological activities and mechanisms of action. Finally, the review deals with future perspectives which include expansion of the structural diversity and bioactivity scope, possible simplification of the structural complexity of the compounds to enhance their drug-likeness, in silico studies, and continuation of the search for new dichapetalins and dichapetalin-type compounds from the over 200 Dichapetalum and over 1200 Phyllanthus species yet to be investigated. It is envisaged that the present review will stimulate further multidisciplinary and interdisciplinary studies. [ABSTRACT FROM AUTHOR]

Cancer, a complex group of heterogeneous diseases characterized by the uncontrolled growth and the capability to invade nearby tissues and organs, represents a severe threat to public health worldwide. Over 100 chemotherapeutics have been approved for clinical cancer therapy, but the goal of eradicating cancer remains elusive mainly due to the continuous emergency of drug resistance, necessitating the development of novel anticancer chemotherapeutics. Indoles and carbazoles, contain a benzo[b]pyrrole moiety, are ubiquitous in nature and possess remarkable structural, and anticancer mechanistic diversity, whereas sulfonamides demonstrated potent anticancer efficacy through multiple modes of action, inclusive of apoptosis induction, autophagy regulation, and cell cycle disruption. Accordingly, indole/carbazole and sulfonamide constitute valuable anticancer pharmacophores, and rational hybridization of sulfonamide and indole/carbazole holds a significant functionality in discovery of new anticancer agents. In this review, we summed up the recent advances of sulfonamide-indole/carbazole hybrids with anticancer potential and elucidated the structure-activity relationships as well as mechanisms of action, covering articles published from 2020 onwards, to pave the way for developing more effective anticancer candidates. [ABSTRACT FROM AUTHOR]

Objective: The main objective of this work is to synthesize thiobarbituric acid based bis-Schiff base derivatives and to evaluate their ability to inhibit urease enzyme and DPPH free radical scavenging potential. Methods: Thiobarbituric acid derived bis-Schiff bases (IIIa–IIIi) were synthesized by treating 2,4-dihydroxybenzaldehyde and the starting moiety 1,3-diethyl-2-thiobarbituric acid in ethanol through refluxed followed by treating chloro ethyl acetate in DMF solvent. Subsequently, hydrazine hydrate was added to compound (II), yielding bis-hydrazide in better yield, which was further reacted via refluxed with benzaldehydes in ethanol, catalyzed by acetic acid to yield compounds (IIIa–IIIi) in excellent yields. Results: The resulting compounds were tested to inhibit urease enzyme and DPPH free radical scavenging activity. Among the series, compound (IIId) (IC50 = 16.11 ± 0.92 µM), (IIIc) (IC50 = 19.11 ± 0.55 µM), and (IIIf) (IC50 = 21.01 ± 1.42 µM) were found as promising lead urease inhibitors, stronger than the standard thiourea (IC50 = 21.15 ± 0.32 µM). Moreover, compound (IIIa) (IC50 = 40.21 ± 0.12 µM) was found as the excellent antioxidant agent comparing it with the standard ascorbic acid. Molecular docking study was performed to analyze the most potent compounds against urease enzyme. The results also shows that all compounds had good ADME properties there was no violation found in compounds ranges all are under druglikness criteria. Additional research combining in vivo, toxicological, and computational analyses can offer thorough understandings of the effectiveness, safety, and fundamental mechanisms of action of these potentially beneficial antioxidant substances. Conclusions: These compounds showed tremendous potential as DPPH free radical scavengers and urease enzyme inhibitors. Compound (IIId) demonstrated the greatest suppression of urease enzyme activity, however compound (IIIa) displayed superior antioxidant effects. Additional research, incorporating in vivo, toxicological, and computational examinations, is necessary to thoroughly assess the effectiveness, safety, and fundamental mechanisms of action of these intriguing antioxidant molecules. [ABSTRACT FROM AUTHOR]

This brief review highlights some of the structure–activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5‐HT2A receptor subtype, a G‐protein coupled receptor known to be the primary target of psychedelics, we refer to several X‐ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions. [ABSTRACT FROM AUTHOR]

The linear undecapeptide BP52 was previously reported to have antibacterial activity against phytopathogenic bacteria species. Due to the structural similarities to naturally occurring cationic helical antimicrobial peptides, it was speculated that this peptide could potentially target microbial pathogens and cancer cells found in mammals. Consequently, this study aims to further investigate the structural and biological properties of this peptide. Our findings indicate that BP52 exhibits strong antimicrobial and anticancer activity while displaying relatively low levels of hemolytic activity. Hence, this study suggests that BP52 could be a potential lead compound for drug discovery against infectious diseases and cancer. Besides, new insights into the relationships between the structure and the multifunctional properties of antimicrobial peptides were also explored. [ABSTRACT FROM AUTHOR]

Many existing research focuses on the differences or performance comparisons between single‐atom or small‐sized nanocluster catalysts, but there is a lack of comprehensive research on the coupling relationship between the structure and activity and the mechanism of synergy. This study investigates the combined catalytic potential of cobalt single atoms (SAs) and nanoclusters (NCs) for enhanced peroxymonosulfate (PMS) activation to degrade norfloxacin (NFX). A novel CoSAs‐NCs/CN/TiO2 catalyst is synthesized, featuring cobalt SAs and NCs uniformly dispersed on the carbon film wrapping TiO2, and the degradation efficiency of the NFX solution is almost completely degraded, with a mineralization rate of 76.35%. Density functional theory (DFT) calculations indicate that the synergistic interaction between cobalt SAs and NCs promotes more efficient PMS adsorption and activation and significantly reduces the activation energy barrier, which enhances electron transfer and increases reactive oxygen species (ROS) generation. This research highlights the robust and versatile nature of this novel catalyst system in addressing various contaminants. This study elucidates the activation mechanism of catalysts, providing new ideas for advanced oxidation processes (AOPs) in environmental remediation, linking the structure and performance of catalysts, and emphasizes the practicality and importance of the CoSAs‐NCs/CN/TiO2 catalyst in effectively and long‐term remediation of water pollutants. [ABSTRACT FROM AUTHOR]

The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFβ, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1β). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway. [Display omitted] In this study, we designed and synthesized a series of benzophenone derivatives targeting NOTCH1, which exhibited anti-inflammatory properties. Notably, the representative derivative D6 demonstrated the ability to promote M2 macrophage polarization while inhibiting M1 polarization, thereby restoring the delicate balance between M1 and M2 immune responses in the treatment of systemic inflammatory response syndrome (SIRS). This effect was primarily attributed to its targeted inhibition of the NOTCH1 signaling pathway at both the transcriptional and mitochondrial levels. Importantly, this discovery unveiled a novel single-target dual-regulatory model involving nuclear transcriptional regulation (NOTCH1/NF-κB/NLRP3/ubiquitination pathway) as well as mitochondrial regulation (NOTCH1/PGC1α pathway). These findings will offer valuable insights for clinical prevention and treatment strategies for SIRS while providing a theoretical foundation for the development of 4-butylbenzophenone derivatives. [ABSTRACT FROM AUTHOR]

Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA®). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The p K a value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox ≥ resveratrol > pterostilbene > tapinarof > pinosylvin ≫ pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4′-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315–399 nm) radiation. In aqueous media at pH 7.4, we observed an ∼50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC 50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 μM, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides. [Display omitted] • Tapinarof, also benvitimod, is redox active moderate electron-donor. • Structure-activity relationship study is presented here with resveratrol analogues. • Tapinarof undergoing irreversible adsorption-driven electrochemical anodic reaction. • The instability of tapinarof could be accelerated by higher temperature or UVA irradiation. • Tapinarof is phototoxic in uM concentration range after UVA irradiation of keratinocytes. [ABSTRACT FROM AUTHOR]

• Perovskite LaZnO 3 photocatalyst was synthesized for SMZ removal under visible light. • Good light absorption and suitable energy levels eased the creation of radicals. • Degradation pathways were unraveled using RP-HPLC/Q-TOF-MS and DFT computation. • Toxicity of SMZ and its intermediates was evaluated using QSAR. In this work, the perovskite LaZnO 3 was synthesized via sol-gel method and applied for photocatalytic treatment of sulfamethizole (SMZ) antibiotics under visible light activation. SMZ was almost completely degraded (99.2% ± 0.3%) within 4 hr by photocatalyst LaZnO 3 at the optimal dosage of 1.1 g/L, with a mineralization proportion of 58.7% ± 0.4%. The efficient performance of LaZnO 3 can be attributed to its wide-range light absorption and the appropriate energy band edge levels, which facilitate the formation of active agents such as · O 2 −, h+, and · OH. The integration of RP-HPLC/Q-TOF-MS and DFT-based computational techniques revealed three degradation pathways of SMZ, which were initiated by the deamination reaction at the aniline ring, the breakdown of the sulfonamide moieties, and a process known as Smile-type rearrangement and SO 2 intrusion. Corresponding toxicity of SMZ and the intermediates were analyzed by quantitative structure activity relationship (QSAR), indicating the effectiveness of LaZnO 3 -based photocatalysis in preventing secondary pollution of the intermediates to the ecosystem during the degradation process. The visible-light-activated photocatalyst LaZnO 3 exhibited efficient performance in the occurrence of inorganic anions and maintained high durability across multiple recycling tests, making it a promising candidate for practical antibiotic treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Acta Materiae Compositae Sinica is the property of Acta Materiea Compositae Sinica Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Poly(ADP-ribose)polymerases (PARPs) have emerged as promising targets for the treatment of diseases, particularly in cancers, due to their significant biological functions involved in DNA damage. As a result, researchers worldwide have made substantial advances in this field. However, studies have revealed that PARPs inhibitors lack selectivity due to the conserved domain, limiting their clinical applications and emphasizing the need for selective inhibitors. In this perspective, we summarize the recent advancements in PARPs inhibitors, with a focus on selective inhibitors among PARP family. We discuss the designed strategy, structure-activity relationships, and crystal structure, while explaining the underlying mechanisms of selectivity, hoping to provide insights for the design of next generation of PARPs selective inhibitors. [ABSTRACT FROM AUTHOR]

This study presents an exploration into the relationship between the molecular structure of oil-soluble fluorinated surfactants and their surface properties across a variety of organic solvents. A series of oil-soluble surfactants with fluorocarbon/hydrocarbon hybrid chains, N-methyl-N-alkyl-4-perfluoroalkylsulfoxybenzylamines (FmHn), were designed and synthesized, and their surface activity was evaluated in 12 organic solvents with different polarities. The surface parameters, including CMC, γ CMC , Γ max and A min , were measured in n-hexadecane, m-xylene, and DMSO, allowing for an in-depth analysis of the influence of molecular structure on these surface properties. Results indicate that an increase in the length of the fluorocarbon chain generally enhances surface activity, leading to a reduction in the CMC value and an increase in the effectiveness of surface tension reduction. However, the impact of the hydrocarbon chain length on surface activity is more complex and dependent on the polarity of the organic solvents. In low-polarity solvents, surface activity is improved with a longer hydrocarbon chain, whereas in high-polarity solvents, a shorter hydrocarbon chain is more beneficial. Consequently, a "polarity–directionality" strategy was proposed to tailor the molecular structure of surfactants to optimize performance in solvents with varying polarities, resulting in a significant reduction in surface tension. Specifically, F8H12 was identified as particularly effective in low-polarity n-alkanes and cycloalkanes, F6H8 was most effective in medium polarity aromatics, and F8H4 or F6H4 was ideal for larger polar solvents. These findings enrich the understanding of the structure–activity relationship in oil-soluble fluorinated surfactants and offer new perspectives for the development of high-performance surfactants with reduced environmental impact. [ABSTRACT FROM AUTHOR]

In order to catalytically degrade organic pollutants, a CoAl-layered double hydroxide catalytic membrane (CoAl-LDH-M) was fabricated for the activation of peroxymonosulfate (PMS). Notably, at the dosage of 50 mg/L PMS and flow rate of 1.0 mL/min, 99.7% removal of Rhodamine B (RhB) was obtained. The corresponding removal efficiency of total organic carbon (TOC) was 59.9%. This demonstrated that CoAl-LDH-M possessed high efficiency for PMS activation. Inductively coupled plasma (ICP) results showed that the leached amount of cobalt and aluminum were 0.13 and 0.04 mg/L, indicating the high stability of CoAl-LDH-M. The CoAl-LDH-M /PMS system could also effectively degrade several other contaminants, obtaining removal efficiencies of 92.7–99.6%. The effects of pH and co-existing ions were investigated as well. Reusability of the catalytic membrane was evaluated in both distilled water and synthetic wastewater. Mechanism studies showed that both reactive oxidative species (ROSs) and non-radical electron transfer were involved. The non-radical electron transfer played the primary role. The degradation pathway of RhB was unraveled by liquid chromatography-mass spectrometry measurements and theoretical calculations. Furthermore, the ecotoxicity of the reaction intermediates was evaluated by utilizing quantitative structure activity relationship (QSAR) calculations. [ABSTRACT FROM AUTHOR]

Human Prk kinase plays an important role in the maintenance of inflammatory stability and has been established as an attractive target of diverse rheumatic immune diseases. The kinase possesses a highly conserved polo-box domain (PBD) in its C-terminal noncatalytic region, which exhibits a wide specificity across its various substrates to regulate the kinase-mediated substrate phosphorylation. In this study, peptide quantitative structure-activity relationship (pQSAR) was systematically modeled based on a gene ontology-enriched set of Prk PBD-binding peptide data, which was structurally characterized using global descriptors and statistically correlated with peptide affinities via both linear and nonlinear machine learning regressions. The optimal pQSAR predictor was then employed to guide the genetic evolution (GE) of a random peptide group toward improved potency to Prk PBD domain, from which a number of hits were measured to have moderate or high affinity. The resulting Pm7 peptide was determined as a good binder that can effectively interact with the domain at sub-micromolar level, which was then used as a parent template to further derive other promising candidates by combining systematic residue mutagenesis and structure-based rescoring. Two Pm7-derived counterparts Pm72 and Pm74 were rationally designed to exhibit a satisfactory binding profile to Prk PBD domain, with affinity improved by 3.1-fold and 4.6-fold relative to their parent Pm7. Structural and energetic analyses revealed that the potent Prk PBD-binding sequences can be divided into a N-terminal polar section, a middle positively charged anchor and a C-terminal hydrophobic section, thus conferring both stability and specificity to the domain-peptide recognition and association. [ABSTRACT FROM AUTHOR]

Since the discovery of the first peroxidase nanozyme (Fe3O4), numerous nanomaterials have been reported to exhibit intrinsic enzyme‐like activity toward inorganic oxygen species, such as H2O2, oxygen, and O2−. However, the exploration of nanozymes targeting organic compounds holds transformative potential in the realm of industrial synthesis. This review provides a comprehensive overview of the diverse types of nanozymes that catalyze reactions involving organic substrates and discusses their catalytic mechanisms, structure‐activity relationships, and methodological paradigms for discovering new nanozymes. Additionally, we propose a forward‐looking perspective on designing nanozyme formulations to mimic subcellular organelles, such as chloroplasts, termed "nano‐organelles". Finally, we analyze the challenges encountered in nanozyme synthesis, characterization, nano‐organelle construction and applications while suggesting directions to overcome these obstacles and enhance nanozyme research in the future. Through this review, our goal is to inspire further research efforts and catalyze advancements in the field of nanozymes, fostering new insights and opportunities in chemical synthesis. [ABSTRACT FROM AUTHOR]

Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hypoxia (low-oxygen) is one of the most common characteristics of solid tumours. Exploiting tumour hypoxia to reductively activate Pt(IV) prodrugs has the potential to deliver toxic Pt(II) selectively and thus overcome the systemic toxicity issues of traditional Pt(II) therapies. However, our current understanding of the behaviour of Pt(IV) prodrugs in hypoxia is limited. Here, we evaluated and compared the aryl carbamate fluorogenic Pt(IV) complexes, CisNap and CarboNap, as well as the previously reported OxaliNap, as potential hypoxia-activated Pt(IV) (HAPt) prodrugs. Low intracellular oxygen concentrations (<0.1%) induced the greatest changes in the respective fluorescence emission channels. However, no correlation between reduction under hypoxic conditions and toxicity was observed, except in the case for CarboNap, which displayed significant hypoxia-dependent toxicity. Other aryl carbamate Pt(IV) derivatives (including non-fluorescent analogues) mirrored these observations, where carboplatin(IV) derivative CarboPhen displayed a hypoxia-selective cytotoxicity similar to that of CarboNap. These findings underscore the need to perform extensive structure activity relationship studies on the cytotoxicity of Pt(IV) complexes under normoxic and hypoxic conditions. [ABSTRACT FROM AUTHOR]

Intestinal inflammatory diseases are increasingly prevalent worldwide, and their pathogenesis is still not fully understood. As of late, studies have discovered that food-derived peptides have specific anti-inflammatory activity and can play a positive role in intestinal health. At the same time, it has broad application prospects in the prevention and treatment of colitis because of its wide source, fast absorption, and high safety. This article reviews the structure-activity and quantity-effect relationships of food-derived peptides for their anti-inflammatory effects. It then discusses their mechanism of action in inhibiting colitis from four aspects. Food-derived anti-inflammatory peptides can delay the progression of the disease by stimulating innate immunity, inhibiting inflammation, and promoting wound healing. Further experiments showed that food-derived anti-inflammatory peptides could prevent and treat colitis through four mechanisms: (a) regulation of inflammatory cytokines; (b) regulation of inflammatory pathways; (c) regulation of intestinal epithelial barrier; (d) regulation of intestinal flora balance. However, due to the treatment of colitis having limitations, there is an urgent to develop food-derived anti-inflammatory peptides as a treatment or adjunctive treatment for colitis. This review highlights the positive effects of food-derived peptides on colitis and anticipates the appearance of mitigating peptides for the therapy of colitis. [ABSTRACT FROM AUTHOR]

2D metal–organic frameworks (2D MOFs) offer promising electrocatalytic potential for urea synthesis, yet the underlying reaction mechanisms and structure‐activity relationships remain unclear. Using Cu‐BDC as a model, density functional theory (DFT) calculations to elucidate these aspects are conducted. The results reveal a novel coupling mechanism involving *NO─CO and *NO─*ONCO, emphasizing the impact of linker modifications on Cu spin states and charge distribution. Notably, Cu‐BDC‐NH2 and Cu─BDC─OH emerge as promising catalysts. Additionally, structure‐activity relationships through descriptors like d‐band center, IE ratio, and L(Cu─O), providing insights for rational catalyst design is established. These findings pave the way for optimized catalysts and sustainable urea production, opening avenues for future research and technological advancements. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the stems of Bridelia stipularis led to the isolation of a new triterpene, 3β-O-trans-feruloylfriedelinol (1), together with five known compounds, friedelin (2), 3β-friedelinol (3), lupeol (4), stigmasterol (5), and 4-(1,5-dimethyl-3-oxo-4-hexenyl)benzoic acid (6). Their structures were identified by intensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance, infrared, and mass spectrometry. Compound 1 showed significant α-glucosidase inhibitory activity (IC50 = 337.49 ± 0.59 µM) close to the standard, acarbose. Furthermore, the structure activity relationship of 1 was analyzed by molecular docking studies. In addition, the molecular docking results showed that the interaction between 1 and the active site occurred through hydrophobic forces and hydrogen bonds. [ABSTRACT FROM AUTHOR]

Uncovering the origin of bifunctional oxygen reduction/evolution reaction (ORR/OER) activity of M-N-C type electrocatalysts is essential for their extensive usage in fuel cells and metal-air batteries. The electrochemical properties of heterogeneous M-N-C catalysts depend on the surface structure, which can be modified via different synthetic methods. Herein, we investigate the effect of structure on the activity of Co–N–C electrocatalyst material derived from an amorphous metal-organic framework TAL-2. Specifically, TAL-2 served as the sole precursor for the synthesis of a range of Co–N–C catalysts via various carbonization and acid-leaching modes. Co–N–C catalysts were prepared by carbonizing TAL-2 at different temperatures (700, 800, 900, and 1000 °C) and subsequent acid-leaching using different acids, namely HCl, H 2 SO 4 , and HNO 3 , either individually or in various combinations. This resulted in the generation of 36 distinct catalyst samples, each exhibiting unique morphological characteristics. By systematically varying these parameters, we aimed to unravel the intricate relationship between post-synthetic treatment and the resulting electrocatalytic properties, shedding light on the rational design of Co–N–C catalysts for enhanced ORR/OER. [Display omitted] • Co–N–C catalysts were derived from TAL-2 MOF by varied post-synthetic treatment. • 36 unique catalysts were studied to understand structure-activity relationships. • Optimized catalysts showed superior ORR/OER performance with low ΔE values. [ABSTRACT FROM AUTHOR]

Direct synthesis of dimethyl carbonate (DMC) from CO2 and CH3OH holds significant economic and environmental value. Numerous catalysts have been employed for this reaction, yet further enhancement of its activity requires a deeper understanding of the catalyst's structure–activity relationship and catalytic mechanism. In this study, we utilized structurally well-defined and highly tunable MOF-808 as a research platform. Functionalizing MOF-808 with ethylenediamine (MOF-808-ED) boosted the space time yield of DMC from 3.25 mmol g−1 h−1 to 7.23 mmol g−1 h−1. The experimental results demonstrate that the reaction involves acid–base synergistic catalysis, where an appropriate balance of acid–base site content is crucial for CO2 and CH3OH to produce DMC, as it facilitates the formation of the key intermediates (CH3OCOO*). Additionally, the nucleophilicity of N is stronger than that of O, further promoting the catalyst's enrichment and activation of CO2. Finally, employing in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) testing, we elucidated the mechanism by which the MOF-808-ED catalyst, with –NH2 as base sites and Zr as acid sites, facilitates the synergistic catalysis of the reaction. This study provides insights into the synergistic effects of acid–base sites on the synthesis of DMC from CO2 and methanol, offering valuable guidance for the development of high-performance catalysts. [ABSTRACT FROM AUTHOR]

With the exponential progress in the field of cheminformatics, the conventional modeling approaches have so far been to employ supervised and unsupervised machine learning (ML) and deep learning models, utilizing the standard molecular descriptors, which represent the structural, physicochemical, and electronic properties of a particular compound. Deviating from the conventional approach, in this investigation, we have employed the classification Read-Across Structure-Activity Relationship (c-RASAR), which involves the amalgamation of the concepts of classification-based quantitative structure-activity relationship (QSAR) and Read-Across to incorporate Read-Across-derived similarity and error-based descriptors into a statistical and machine learning modeling framework. ML models developed from these RASAR descriptors use similarity-based information from the close source neighbors of a particular query compound. We have employed different classification modeling algorithms on the selected QSAR and RASAR descriptors to develop predictive models for efficient prediction of query compounds' hepatotoxicity. The predictivity of each of these models was evaluated on a large number of test set compounds. The best-performing model was also used to screen a true external data set. The concepts of explainable AI (XAI) coupled with Read-Across were used to interpret the contributions of the RASAR descriptors in the best c-RASAR model and to explain the chemical diversity in the dataset. The application of various unsupervised dimensionality reduction techniques like t-SNE and UMAP and the supervised ARKA framework showed the usefulness of the RASAR descriptors over the selected QSAR descriptors in their ability to group similar compounds, enhancing the modelability of the dataset and efficiently identifying activity cliffs. Furthermore, the activity cliffs were also identified from Read-Across by observing the nature of compounds constituting the nearest neighbors for a particular query compound. On comparing our simple linear c-RASAR model with the previously reported models developed using the same dataset derived from the US FDA Orange Book (https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm), it was observed that our model is simple, reproducible, transferable, and highly predictive. The performance of the LDA c-RASAR model on the true external set supersedes that of the previously reported work. Therefore, the present simple LDA c-RASAR model can efficiently be used to predict the hepatotoxicity of query chemicals. [ABSTRACT FROM AUTHOR]

AbstractNew approach methodologies (NAMs) offer information tailored to the intended application while reducing the use of animals. NAMs aim to develop quantitative structure-activity relationship (QSAR) and quantitive-Read-Across structure-activity relationship (q-RASAR) models to predict and categorize the acute toxicity of known and unknown endocrine-disrupting chemicals (EDCs) against zebrafish. EDCs are a diverse group of toxic substances that disrupt the endocrine system of humans and animals. The q-RASAR model was constructed and verified using validation metrics (R2 = 0.886 and Q2 = 0.814) which found to be more reliable model compare to QSAR model. The substructure fingerprint was well-fitted for the classification model and it was validated using 10-fold average accuracy (Q = 86.88%), specificity (Sp = 88.89%), Matthew’s correlation curve (MCC = 0.621) and receiver operating characteristics (ROC = 0.828). The dataset of unknown substances revealed that phenolphthalein (Php) exhibited a significant level of toxicity based on q-RASAR model. The docking and simulation study indicated that the computationally derived important features successfully bound to the target zebrafish sex hormone binding globulin (zfSHBG). The experimental LC50 value of 0.790 mg L−1 was very close to the predicted value of 0.763 mg L−1, which provides high confidence to the developed model. [ABSTRACT FROM AUTHOR]

The development of readily accessible and interpretable descriptors is pivotal yet challenging in the rational design of metal–organic framework (MOF) catalysts. This study presents a straightforward and physically interpretable activity descriptor for the oxygen evolution reaction (OER), derived from a dataset of bimetallic Ni‐based MOFs. Through an artificial‐intelligence (AI) data‐mining subgroup discovery (SGD) approach, a combination of the d‐band center and number of missing electrons in eg states of Ni, as well as the first ionization energy and number of electrons in eg states of the substituents, is revealed as a gene of a superior OER catalyst. The found descriptor, obtained from the AI analysis of a dataset of MOFs containing 3–5d transition metals and 13 organic linkers, has been demonstrated to facilitate in‐depth understanding of structure–activity relationship at the molecular orbital level. The descriptor is validated experimentally for 11 Ni‐based MOFs. Combining SGD with physical insights and experimental verification, our work offers a highly efficient approach for screening MOF‐based OER catalysts, simultaneously providing comprehensive understanding of the catalytic mechanism. [ABSTRACT FROM AUTHOR]

Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase within the insulin receptor superfamily. Alterations in ALK, such as rearrangements, mutations, or amplifications, have been detected in various tumours, including lymphoma, neuroblastoma, and non-small cell lung cancer. In this study, we outline a computational workflow designed to uncover new inhibitors of ALK. This process starts with a ligand-based exploration of the pharmacophoric space using 13 diverse sets of ALK inhibitors. Subsequently, quantitative structure-activity relationship (QSAR) modelling is employed in combination with a genetic function algorithm to identify the optimal combination of pharmacophores and molecular descriptors capable of elucidating variations in anti-ALK bioactivities within a compiled list of inhibitors. The successful QSAR model revealed three pharmacophores, two of which share three similar features, prompting their merger into a single pharmacophore model. The merged pharmacophore was used as a 3D search query to mine the National Cancer Institute (NCI) database for novel anti-ALK leads. Subsequent in vitro bioassay of the top 40 hits identified two compounds with low micromolar IC50 values. Remarkably, one of the identified leads possesses a novel chemotype compared to known ALK inhibitors. [ABSTRACT FROM AUTHOR]

Prion diseases are 100% fatal infectious neurodegenerative diseases affecting the brains of humans and other mammals. The disease is caused by the formation and replication of prions, composed exclusively of the misfolded prion protein (PrPSc). We invented and developed the protein misfolding cyclic amplification (PMCA) technology for in vitro prion replication, which allow us to replicate the infectious agent and it is commonly used for ultra-sensitive prion detection in biological fluids, tissues and environmental samples. In this article, we studied whether PMCA can be used to screen for chemical compounds that block prion replication. A small set of compounds previously shown to have anti-prion activity in various systems, mostly using cells infected with murine prions, was evaluated for their ability to prevent the replication of prions. Studies were conducted simultaneously with prions derived from 4 species, including human, cattle, cervid and mouse. Our results show that only one of these compounds (methylene blue) was able to completely inhibit prion replication in all species. Estimation of the IC50 for methylene blue inhibition of human prions causing variant Creutzfeldt-Jakob disease (vCJD) was 7.7 μM. Finally, we showed that PMCA can be used for structure-activity relationship studies of anti-prion compounds. Interestingly, some of the less efficient prion inhibitors altered the replication of prions in some species and not others, suggesting that PMCA is useful for studying the differential selectivity of potential drugs. [ABSTRACT FROM AUTHOR]

Background: Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite Strongyloides venezuelensis yielded meager success rates. This situation is reminiscent of Gram-negative bacteria, where drug entry is a limiting factor. Methods: Here, we set out to determine whether similar barriers are in place and establish whether structural and property requirements exist for anti-strongyloides drug discovery. We focused on dyes as their uptake and effects on viability can be independently assessed in the multicellular parasite, thus providing a means to study the possibility of similar entry rules. We tested different dyes in in vitro assays on L3s. Results: We found that staining was necessary to reduce parasite viability, with some dyes achieving anti-strongyloides effects at concentrations similar to those of the reference drug, ivermectin (IV). Some dyes also showed activity against female adults at concentrations well below that of ivermectin. Unfortunately, the most potent dye, Methylene Blue, was unable to prevent the infection in a preliminary in vivo mouse model assay, presumably due to fast dye clearance. Structural analysis showed that positive charges facilitated the access of the compounds to the L3 tissue, thus providing a structural tool for the introduction of activity. For female adults, low globularity is additionally required. As a proof of concept, we added a positive charge to an inactive compound of one of our chemical libraries and re-determined the activity. Conclusions: These findings allow us to establish structural rules for parasite entry that could be of interest for future drug screening or drug development campaigns. These rules might also be applicable to other related parasites. [ABSTRACT FROM AUTHOR]

A series of 2-[(2,6-diarylpiperidin-4-yl)hydrazono]-2,3-dihydrothiazoles (25–40) were synthesized by the reaction of respective thiosemicarbazones (9–24) with phenacyl bromide in the presence of sodium acetate-acetic acid buffer and refluxing in ethanol for 12–16 h. The newly synthesized target compounds were characterized by elemental analysis, mass, FT-IR, 1H and 13C NMR spectroscopic methods. A Structure activity relationship study was carried out for the title compounds against a panel of bacterial strains viz Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Bacillus subtilis and Klebsiella pneumonia and the fungal strains Cryptococcus neoformans, Candida albicans, Rhizopus sp, Aspergillus niger and Aspergillus flavus, respectively, using ciprofloxacin and amphotericin-B as standard drugs. These studies proved that compounds 26 and 34 against Staphylococcus aureus, 35 against P. aeruginosa,38 against B. subtilis, and 27 against K. pneumonia showed maximum inhibitory potency at the lowest concentration (6.25 µg/mL), whereas 26, 34 and 35 against C. neoformans and 26 and 27 against Candida albicans showed beneficial antifungal activity at a minimum concentration (MIC) of 6.25 µg/mL. [ABSTRACT FROM AUTHOR]

In this work, it is designed and synthesized therapeutically active anti-urease agents based on 3-bromosulfanilamide-based acyl thioureas (4a-j) through reaction of brominated sulfanilamide with aromatic acids via isothiocyanate formation and characterized by using FT-IR, 1HNMR, 13C NMR and MS analysis. The freshly prepared compounds were screened for in vitro urease inhibition assay. The derivative 4a with an un-substituted phenyl group showed IC50 value of 17.02 ± 0.011 against urease as compared to the standard thiourea (IC50 = 21 ± 0.12 µM). Structure activity relationship (SAR) revealed that the electronic and positional effects of substituents on phenyl ring play important role for the inhibition of clinically important enzymes. Additionally, in silico investigation was carried out which demonstrated that the compounds have exhibited polar and nonpolar interaction with the crucial residues in the binding site of urease. The in vitro and in silico studies are in agreement as per kinetics and docking results indicating that the synthesized 3-bromosulfanilamide-based acyl thiourea derivatives may serve as potential hits for the discovery of new urease inhibitors. [ABSTRACT FROM AUTHOR]