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We previously reported trisubstituted pyrimidine lead compounds, namely, ARN22089 and ARN25062, which block the interaction between CDC42 with its specific downstream effector, a PAK protein. This interaction is crucial for the progression of multiple tumor types. Such inhibitors showed anticancer efficacy in vivo. Here, we describe a second class of CDC42 inhibitors with favorable drug-like properties. Out of the 25 compounds here reported, compound 15 (ARN25499) stands out as the best lead compound with an improved pharmacokinetic profile, increased bioavailability, and efficacy in an in vivo PDX tumor mouse model. Our results indicate that these CDC42 inhibitors represent a promising chemical class toward the discovery of anticancer drugs, with ARN25499 as an additional lead candidate for preclinical development.

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host's native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families-a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases-from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure-activity relationship, and will thus enable the rational design of potent vaccine adjuvants.

Here, an in vitro characterization of a family of prazole derivatives that covalently bind to the C73 site on Tsg101 and assay their ability to inhibit viral particle production is presented. Structurally, increased steric bulk on the 4-pyridyl of the prazole expands the prazole site on the UEV domain toward the β-hairpin in the Ub-binding site and is coupled to increased inhibition of virus-like particle production in HIV-1. Increased bulk also increased toxicity, which is alleviated by increasing flexibility. Further, the formation of a novel secondary Tsg101 adduct for several of the tested compounds and the commercial drug lansoprazole. The secondary adduct involved the loss of the 4-pyridyl substituent to form an irreversible species, with implications for increasing the half-life of the active species or its specificity toward Tsg101 UEV. It is also determined that sulfide derivatives display effective viral inhibition, presumably through cellular sulfoxidation, allowing for delayed conversion within the cellular environment, and identify SARS-COV-2 as a target of prazole inhibition. These results open multiple avenues for the design of prazole derivatives for antiviral applications.

The synthesis of a novel disorazole C1 analogue is described, and its biological activity as a cytotoxic compound is reported. Based on our convergent and flexible route to the disorazole core, we wish to report a robust strategy to synthesize a non-symmetrical disorazole in which we couple one half of the molecule containing the naturally occurring oxazole heterocycle and the second half of the disorazole macrocycle containing a thiazole heterocycle. This resulted in a very unusual non-symmetrical disorazole C1 analogue containing two different heterocycles, and its biological activity was studied. This provided exciting information about SAR (structure-activity-relationship) for this highly potent class of antitumor compounds.

Lipid nanoparticles (LNPs) are being intensively researched and developed to leverage their ability to safely and effectively deliver therapeutics. To achieve optimal therapeutic delivery, a comprehensive understanding of the relationship between formulation, structure, and efficacy is critical. However, the vast chemical space involved in the production of LNPs and the resulting structural complexity make the structure to function relationship challenging to assess and predict. New components and formulation procedures, which provide new opportunities for the use of LNPs, would be best identified and optimized using high-throughput characterization methods. Recently, a high-throughput workflow, consisting of automated mixing, small-angle X-ray scattering (SAXS), and cellular assays, demonstrated a link between formulation, internal structure, and efficacy for a library of LNPs. As SAXS data can be rapidly collected, the stage is set for the collection of thousands of SAXS profiles from a myriad of LNP formulations. In addition, correlated LNP small-angle neutron scattering (SANS) datasets, where components are systematically deuterated for additional contrast inside, provide complementary structural information. The centralization of SAXS and SANS datasets from LNPs, with appropriate, standardized metadata describing formulation parameters, into a data repository will provide valuable guidance for the formulation of LNPs with desired properties. To this end, we introduce Simple Scattering, an easy-to-use, open data repository for storing and sharing groups of correlated scattering profiles obtained from LNP screening experiments. Here, we discuss the current state of the repository, including limitations and upcoming changes, and our vision towards future usage in developing our collective knowledge base of LNPs.

Bovine mastitis is a worldwide disease affecting dairy cattle and causes major economic losses in the dairy industry. Recently, the emergence of microbial resistance to the current antibiotics complicates the treatment protocol which necessitates antibiotic stewardship and further research to find new active compounds. Recently, phytobiotics have gained interest in being used as an alternative to antibiotics in the poultry industry as an antibiotic stewardship intervention. This study evaluated the in vitro antibacterial activity of 16 flavonoids against bovine mastitis pathogens. Two flavones: 2-(4-methoxyphenyl)chromen-4-one (1) and 2-(3-hydroxyphenyl)chromen-4-one (4) showed inhibition of the growth of Klebsiella oxytoca with MIC values range (25–50 µg mL− 1) followed by a structure-activity relationship (SAR) study indicating that the presence of a hydroxyl group at C-3' or methoxy at C-4' increases the activity against Klebsiella oxytoca while the presence of hydroxyl group at C-7 decreases the activity. Furthermore, a structure-based drug development approach was applied using several in silico tools to understand the interactions of active flavones at the active site of the DNA gyrase protein. Compound (4) showed a higher docking score than quercetin (standard) which is known to have antibacterial activity by inhibiting the DNA gyrase. In addition, the structure-based pharmacophores of compound (4) and quercetin showed similar pharmacophoric features and interactions with DNA gyrase. Based on our findings, compounds (1) and (4) are promising for further study as potential anti-microbial phytochemicals that can have a role in controlling bovine mastitis as well as to investigate their mechanism of action further. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ni phyllosilicate was firstly synthesized by a modified microwave synthesis method. • Surfactant modification led to ultrahigh specific surface area of 535 m2 g−1 and ultrathin layer of Ni phyllosilicate of only 1.43 nm. • Hexadecyl trimethyl ammonium bromide showed higher promotion effect compared with P123 and F127. • The special structure resulted in competitive catalytic activity for CO 2 methanation. • This catalyst could exhibit high stability for 100 h in a long-term test. The traditional techniques for the synthesis of nickel phyllosilicates usually time-consuming and energy-intensive, which often lead to the formation of layers with excessive thickness due to uncontrolled crystal growth. In order to overcome these challenges, this work introduces a microwave-assisted synthesis strategy to facilitate the synthesis of Ni-phyllosilicate-based catalysts within an exceptionally short duration of only five minutes, attaining a peak temperature of merely 102 °C. To enhance the specific surface area and to increase the exposure of active sites, an investigation was conducted involving three surfactants. The employment of hexadecyl trimethyl ammonium bromide (CTAB) has yielded remarkable results, with an ultrahigh specific surface area reaching 535 m2 g−1 and an ultrathin lamellar thickness of 1.43 nm. The catalyst exhibited an impressive CO 2 conversion of 81.7 % at 400 °C, 60 L g−1 h−1, 0.1 MPa. It also demonstrated a substantial turnover frequency for CO 2 (TOF CO2) of 5.4 ± 0.1 × 10−2 s−1, alongside a relatively low activation energy (E a) of 80.74 kJ·mol−1. Moreover, the catalyst maintained its high stability over a period of 100 h and displayed high resistance to sintering. To further elucidate growth temperature gradient of the catalyst and concentration gradient of the materials involved, COMSOL Multiphysics (COMSOL) simulations were effectively utilized. In conclusion, this work breaks the limitation associated with traditional, laborious synthesis methods for Ni-phyllosilicates, which can produce materials with high surface area and thin-layer characteristics. [ABSTRACT FROM AUTHOR]

As temperature and salt-resistant materials, hydrophobically associating polymers can form a reversible spatial network structure through the interaction between their hydrophobic groups, effectively improve the viscosity of the polymer solution through association, and enhance the temperature and salt resistance of the polymer. Hydrophobically associating monomers have different effects on the properties of polymer solutions. Herein, acrylic acid, acrylamide, and 2-acrylamido-2-methylpropanesulfonic acid were used as hydrophilic monomers. The three hydrophobic monomers with different carbon chain lengths were prepared by the bromination reaction. Hydrophobic associating polymers DQM1-PAM, DQM2-PAM, and DQM3-PAM were prepared by aqueous solution free-radical polymerization. The structure–activity relationship of the hydrophobic monomers with different carbon chain lengths on polymers was studied. It was confirmed by Fourier-transform infrared spectroscopy and 1H-NMR that the target product was successfully synthesized. Scanning electron microscopy revealed that with increasing hydrophobic carbon chain length, the hydrophobic microarea of molecular aggregation increased, forming a closer spatial network structure. Thermogravimetric and fluorescence tests revealed that with increasing hydrophobic carbon chain length of polymer molecules, the polymerization temperature resistance increased, intermolecular association degree increased, and critical association concentration decreased. Rheological property evaluation revealed that the viscosity of 0.5% polymer DQM1-PAM, DQM2-PAM, and DQM3-PAM was 71.32, 100.21, and 118.79 mPa·s after shearing at 120 °C and 170 s−1 for 1 h. With the increase in the carbon chain length, the retention rate of shear viscosity of polymer in a salt solution increased, showing good salt resistance. Concurrently, the molecular aggregation microarea of a solution with 0.5% polymer, degree of molecular chain action, viscoelasticity of the solution (G' > G''), and thixotropic area all increased. The performance of polymer solution can be improved by modifying hydrophobically associating polymers with long carbon chains, which has a broader application. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are responsible for significant mortality rates globally that have been raised due to the limitation of the available treatments and prevalence of CVDs. The innovative research and identification of potential preventives for CVDs are essential to alleviate global deaths and complications. The marine environment is a rich source of bioactive substances and provides a unique chemical arsenal against numerous ailments due to its unrivaled biodiversity. Marine polyphenolic compounds (MPCs) are unique because of their structural variety and biologically significant activity. Further, MPCs are well-reported for their valuable biological activities, such as anti-inflammatory, cardioprotective, and antioxidant, demonstrating encouraging results in preventing and treating CVDs. Therefore, investigation of the structure–activity relationship (SAR) between MPCs and CVDs provides insights that reveal how the structural components of these compounds affect their effectiveness. Further, comprehending this correlation is essential for advancing medications and nutraceuticals sourced from marine sources, which could transform the strategy for treating and preventing cardiovascular diseases. Therefore, this study provides a comprehensive analysis of existing research by emphasizing the role of MPCs in CVD treatments and evaluating the SAR between MPCs and CVDs with challenges and future directions. [ABSTRACT FROM AUTHOR]

In our ongoing work to create potential antifungal agents, we synthesized and tested a group of C1-substituted acylhydrazone β-carboline analogues 9a–o and 10a–o for their effectiveness against Valsa mali, Fusarium solani, Fusarium oxysporum, and Fusarium graminearum. Their compositions were analyzed using different spectral techniques, such as 1H/13C NMR and HRMS, with the structure of 9l being additionally confirmed through X-ray diffraction. The antifungal evaluation showed that, among all the target β-carboline analogues, compounds 9n and 9o exhibited more promising and broad-spectrum antifungal activity than the commercial pesticide hymexazol. Several intriguing findings regarding structure–activity relationships (SARs) were examined. In addition, the cytotoxicity test showed that these acylhydrazone β-carboline analogues with C1 substitutions exhibit a preference for fungi, with minimal harm to healthy cells (LO2). The reported findings provide insights into the development of β-carboline analogues as new potential antifungal agents. [ABSTRACT FROM AUTHOR]

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 μg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 μg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 μg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 μg/mL). The structure–activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents. [ABSTRACT FROM AUTHOR]

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office 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.)

Hyperuricemia (HUA), or elevated uric acid in the blood, has become more prevalent in recent years. Polyphenols, which are known to have good inhibitory activity on xanthine oxidoreductase (XOR), are effective in uric acid reduction. In this review, we address the structure–activity relationship of flavonoids that inhibit XOR activity from two perspectives: the key residues of XOR and the structural properties of flavonoids. Flavonoids' inhibitory effect is enhanced by their hydroxyl, methoxy, and planar structures, whereas glycosylation dramatically reduces their activity. The flavonoid structure–activity relationship informed subsequent discussions of the changes that occur in polyphenols' XOR inhibitory activity during their extraction, processing, gastrointestinal digestion, absorption, and interactions. Furthermore, gastrointestinal digestion and heat treatment during processing can boost the inhibition of XOR. Polyphenols with comparable structures may have a synergistic effect, and their synergy with allopurinol thus provides a promising future research direction. [ABSTRACT FROM AUTHOR]

Introduction: Despite the rising concern with fungal resistance, a myriad of molecules has yet to be explored. Geraniol, linalool, and citronellal are monoterpenes with the same molecular formula (C10H18O), however, neither the effect of these compounds on inflammatory axis induced by Candida spp. nor the antibiofilm Structure-Activity Relationship (SAR) have been well-investigated. Herein we analyzed geraniol, linalool and citronellal antifungal activity, cytotoxicity, and distinctive antibiofilm SAR, also the influence of geraniol on Candida spp induced dysregulated inflammatory axis, and in vivo toxicity. Methods: Minimal inhibitory (MIC) and fungicidal (MFC) concentrations against Candida spp were defined, followed by antibiofilm activity (CFU-colony forming unit/mL/g of dry weight). Cytotoxic activity was assessed using human monocytes (THP-1) and oral squamous cell (TR146). Geraniol was selected for further analysis based on antifungal, antibiofilm and cytotoxic results. Geraniol was tested using a dual-chamber co-culture model with TR146 cells infected with C. albicans, and THP-1 cells, used to mimic oral epithelium upon fungal infection. Expression of Candida enzymes (phospholipase-PLB and aspartyl proteases-SAP) and host inflammatory cytokines (interleukins: IL-1ß, IL-6, IL-17, IL-18, IL-10, and Tumor necrosis factor-TNF) were analyzed. Lastly, geraniol in vivo toxicity was assessed using Galleria mellonella. Results: MIC values obtained were 1.25-5 mM/mL for geraniol, 25-100 mM/mL for linalool, and 100-200 mM/mL for citronellal. Geraniol 5 and 50 mM/mL reduced yeast viability during biofilm analysis, only 500 mM/mL of linalool was effective against a 72 h biofilm and no biofilm activity was seen for citronellal. LD50 for TR146 and THP-1 were, respectively: geraniol 5.883 and 8.027 mM/mL; linalool 1.432 and 1.709 mM/mL; and citronellal 0.3006 and 0.1825 mM/mL. Geraniol was able to downregulate expression of fungal enzymes and host proinflammatory cytokines IL-1ß, IL-6, and IL-18. Finally, safety in vivo parameters were observed up to 20 mM/Kg. Discussion: Despite chemical similarities, geraniol presented better antifungal, antibiofilm activity, and lower cytotoxicity when compared to the other monoterpenes. It also showed low in vivo toxicity and capacity to downregulate the expression of fungal enzymes and host pro-inflammatory cytokines. Thus, it can be highlighted as a viable option for oral candidiasis treatment. [ABSTRACT FROM AUTHOR]

AbstractLactic acid bacteria (LAB) are the main probiotics currently available in the markets and are essential for maintaining gut health. To guarantee probiotic function, it is imperative to boost the culture yield of probiotic organisms, ensure the sufficient viable cells in commercial products, or develop effective prebiotics. Recent studies have shown that protein hydrolysates and their derived peptides promote the proliferation of probiotic in vitro and the abundance of gut flora. This article comprehensively reviews different sources of protein hydrolysates and their derived peptides as growth-promoting factors for probiotics including Lactobacillus, Bifidobacterium, and Saccharomyces. We also provide a preliminary analysis of the characteristics of LAB proteolytic systems focusing on the correlation between their elements and growth-promoting activities. The structure-activity relationship and underlying mechanisms of growth-promoting peptides and their research perspectives are thoroughly discussed. Overall, this review provides valuable insights into growth-promoting protein hydrolysates and their derived peptides for proliferating probiotics in vivo or in vitro, which may inspire researchers to explore new options for industrial probiotics proliferation, dairy products fermentation, and novel prebiotics development in the future. [ABSTRACT FROM AUTHOR]

The extent to which electrophores covalently bridged by a saturated linker are electrochemically independent was investigated considering the charge/spin duality of the electron and functionality of the electrophore as a spin carrier upon reduction. By combining computational modeling with electrochemical experiments, we investigated the mechanism by which tethered electrophores react together within 4,4′‐oligo[n]methylene‐bipyridinium assemblies (with n=2 to 5). We show that native dicationic electrophores (redox state Z=+2) are folded prior to electron injection into the system, allowing the emergence of supra‐molecular orbitals (supra‐MOs) likely to support the process of the reductive σ bond formation giving cyclomers. Indeed, for Z=+2, London Dispersion (LD) forces contribute to flatten the potential energy surface such that all‐trans and folded conformers are approximately isoenergetic. Then, upon one‐electron injection, for radical cations (Z=+1), LD forces significantly stabilize the folded conformers, except for the ethylene derivative deprived of supra‐MOs. For radical cations equipped with supra‐MOs, the unpaired electron is delocalized over both heterocycles through space. Cyclomer completion (Z=0) upon the second electron transfer occurs according to the inversion of redox potentials. This mechanism explains why intramolecular reactivity is favored and why pyridinium electrophores are not independent. [ABSTRACT FROM AUTHOR]

Hydrogen‐bonded frameworks have garnered significant attention due to their flexible structures with tailored porosity, making them a promising class of porous framework materials. However, the direct synthesis of hydrogen‐bonded frameworks with specific functions is highly challenging due to the unpredictable formation of hydrogen‐bonded frameworks. In response, postsynthetic modification has emerged as a potent strategy to imbue desired functions into hydrogen‐bonded frameworks. Recent advances have demonstrated the effectiveness of postsynthetic modification in hydrogen‐bonded frameworks for studying their mechanical, luminescent, electrochemical, and chiral properties. In this concept, we comprehensively summarize the methodologies and outcomes of postsynthetic modification to hydrogen‐bonded frameworks, providing a highlight of this exciting research area. [ABSTRACT FROM AUTHOR]

Prolyl oligopeptidase (POP) is a conserved serine protease belonging to proline-specific peptidases. It has both enzymatic and non-enzymatic activity and is involved in numerous biological processes in the human body, playing a role in e.g., cellular growth and differentiation, inflammation, as well as the development of some neurodegenerative and neuropsychiatric disorders. This article describes the physiological and pathological aspects of POP activity and the state-of-art of its peptidic inhibitors originating from food proteins, with a particular focus on their potential as cognition-enhancing agents. Although some milk, meat, fish, and plant protein-derived peptides have the potential to be applied as natural, procognitive nutraceuticals, their effectiveness requires further evaluation, especially in clinical trials. We demonstrated that the important features of the most promising POP-inhibiting peptides are very short sequence, high content of hydrophobic amino acids, and usually the presence of proline residue. [ABSTRACT FROM AUTHOR]

Quasi‐one‐dimensional (quasi‐1D) van der Waals crystal fibrous red phosphorus (RP) exhibits pronounced in‐plane optical anisotropy, positioning it as a potential candidate for polarization‐related micro‐nano devices. Unfortunately, a comprehensive investigation into the complex refractive index of fibrous RP and the structure–activity relationship connecting the distinctive quasi‐1D structure with optical anisotropy is currently deficient. Herein, we have collectively determined the complex refractive index of the fibrous RP flakes within the ab‐plane through Kramers–Kronig (KK) analysis and theoretical calculation. Notably, the maximum birefringence of fibrous RP reaches 0.642@475 nm with an absolute extinction coefficient of only 0.08, superior to the reported traditional optical crystals and the emerging low‐dimensional materials as well. The remarkable birefringence can be attributed to the synergistic influence of the large electronic dipole polarizability, anisotropic electron density distribution and the distortion of stereochemically active lone pair (SCALP). This work demonstrates the potential of fibrous RP for polarization‐sensitive devices, illuminating possibilities to exploit novel giant birefringent crystals based on the structure–activity relationship. [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]

Copyright of Shipin Kexue/ Food Science is the property of Food Science 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.)

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]

Herein we report the synthesis and biological evaluation of a new series of thiazolidin-4-one derivatives. The C4 and C5 functionalized, 5-arylidene/alkylidene, 5-bromo, 5-pyridinium, and 4-arylimino analogs of thiazolidine-4-one were prepared efficiently using appropriate synthetic routes and characterized by IR, NMR and Mass spectrometry. Results of antimicrobial evaluation showed that compounds 4 and 8 had significant antibacterial activity comparable to that of the reference drug gentamicin. Compound 5a showed promising antifungal activity compared to amphotericin B as a reference drug. The antitumor activity revealed that compound 4 was the most active analog among the tested series with IC50 values of 28.4 and 12.6 µg/mL against both HCT-116 and HepG-2 cell lines, respectively, compared to standard drug doxorubicin. Results from the biological evaluation, in-silico molecular docking studies, and ADMET analyses confirmed that thiazolidin-4-one is a promising scaffold that can be used to design potential lead compounds for the antibacterial and antitumor agents. [ABSTRACT FROM AUTHOR]

This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action. This review focuses on metallodrugs that contain a metal as a key structural fragment, with cisplatin paving the way for their chemotherapeutic application. The text also looks at ruthenium complexes, including the therapeutic applications of phosphorescent ruthenium(II) complexes, emphasizing their dual role in therapy and diagnostics. In addition, the antitumor activities of titanium and gold derivatives, their side effects, and ongoing research to improve their efficacy and reduce adverse effects are discussed. Metallization of host defense peptides (HDPs) with various metal ions is also highlighted as a strategy that significantly enhances their anticancer activity by broadening their mechanisms of action. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the structure-activity relationship between cannabinoid and opioid ligands with models of cannabinoid and opioid receptors. There are differences in the mechanisms of pain control for these two types of receptors, but targeting the creation of compounds that bind to both opioid and cannabinoid receptors lead to more effective solving of this problem. This will lead to the development of new and improved strategies to prevent opiate addiction and its consequences. [ABSTRACT FROM AUTHOR]

Blood pressure and fluid balance are regulated hormonally by renin-angiotensin system (RAS). Influence on this system could be achieved by different compounds that act as angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers and renin inhibitors. The purpose of the present study is to predict the structures of the potent ACE inhibitors on the base of His-Leu peptide structural element of angiotensine I using computational methods. Different modifications were made in the structure of this dipeptide and the energy of binding with the enzyme were calculated. The docking results were analyzed and it was found that along with the important amino acid residue of the receptor molecule Arg167, the Tyr residues (35, 87, 88 and 92) as well as Cys180 are extremely important for the strong binding to the receptor and, accordingly, the manifestation of antagonistic action by the analogues. To block the receptor, the ligand molecule must have an intact terminal carboxyl group and an imidazole nucleus to participate in appropriate interactions. The inclusion of functional groups in the side chains of the amino acid residues of the dipeptide create an additional site for binding to the receptor. With the help of docking, the ligand molecule can be optimized, and this process is fast, saving the synthesis of many compounds and their biological testing. And finally, the most potent analogues will be synthesized and biologically tested. [ABSTRACT FROM AUTHOR]

CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity. [ABSTRACT FROM AUTHOR]

The majority of the immune cell population in the tumor microenvironment (TME) consists of tumor-associated macrophages (TAM), which are the main players in coordinating tumor-associated inflammation. TAM has a high plasticity and is divided into two main phenotypes, pro-inflammatory M1 type and anti-inflammatory M2 type, with tumor-suppressive and tumor-promoting functions, respectively. Considering the beneficial effects of M1 macrophages for anti-tumor and the high plasticity of macrophages, the conversion of M2 TAM to M1 TAM is feasible and positive for tumor treatment. This study sought to evaluate whether the glycopeptide derived from simulated digested Codonopsis pilosula extracts could regulate the polarization of M2-like TAM toward the M1 phenotype and the potential regulatory mechanisms. The results showed that after glycopeptide dCP1 treatment, the mRNA relative expression levels of some M2 phenotype marker genes in M2-like TAM in simulated TME were reduced, and the relative expression levels of M1 phenotype marker genes and inflammatory factor genes were increased. Analysis of RNA-Seq of M2-like TAM after glycopeptide dCP1 intervention showed that the gene sets such as glycolysis, which is associated with macrophage polarization in the M1 phenotype, were significantly up-regulated, whereas those of gene sets such as IL-6-JAK-STAT3 pathway, which is associated with polarization in the M2 phenotype, were significantly down-regulated. Moreover, PCA analysis and Pearson's correlation also indicated that M2-like TAM polarized toward the M1 phenotype at the transcriptional level after treatment with the glycopeptide dCP1. Lipid metabolomics was used to further explore the efficacy of the glycopeptide dCP1 in regulating the polarization of M2-like TAM to the M1 phenotype. It was found that the lipid metabolite profiles in dCP1-treated M2-like TAM showed M1 phenotype macrophage lipid metabolism profiles compared with blank M2-like TAM. Analysis of the key differential lipid metabolites revealed that the interconversion between phosphatidylcholine (PC) and diacylglycerol (DG) metabolites may be the central reaction of the glycopeptide dCP1 in regulating the conversion of M2-like TAM to the M1 phenotype. The above results suggest that the glycopeptide dCP1 has the efficacy to regulate the polarization of M2-like TAM to M1 phenotype in simulated TME. [ABSTRACT FROM AUTHOR]

Copyright of Natural Gas Industry is the property of Natural Gas Industry Journal Agency 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.)

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6′-N-acetyltransferase type I enzyme, of which type Ib [AAC(6′)-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive for drug development. Mixture-based combinatorial libraries and positional scanning strategy have led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1–R5), inhibits AAC(6′)-Ib-mediated inactivation of amikacin. Structure–activity relationship studies have shown that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003, reduced inhibition levels, demonstrating the essential nature not only of the presence of an S-phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions had varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of the compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity. [ABSTRACT FROM AUTHOR]

Phytocoumarins exhibit a range of biological activities, including antibacterial, anti-inflammatory, antiradical, oncolytic, and reduction of monoamine oxidase B effects. These compounds are frequently used by researchers to develop novel, entirely or partially laboratory-made pharmaceutical medicines derived from coumarin. Several of these medications are hybrid chemicals with different pharmacological effects that were purposefully created by applying the molecular hybridization concept. The combinations of compounds exhibit multifunctional characteristics, making them attractive options for developing therapies against complex diseases like cancer, Alzheimer's disease, dysmetabolic syndrome, AIDS, plasmodium infection, and cardiovascular disorders. This study summarizes findings on the development of various coumarin hybrids, groups them based on prospective therapeutic uses, and makes recommendations about possible structure–activity relationships. We searched a number of database servers, including PubMed, Scopus, Google Scholar, Web of Science, and others. Following a sieve, we eventually found and incorporated 45 relevant papers that were released between 2004 and the beginning of 2024. In order to help medicinal chemists cure a range of human ailments, the authors set out to create and produce highly efficient, tailored coumarin hybrid molecules. [ABSTRACT FROM AUTHOR]

Jujube has a history of being used as both food and herbal medicine in China for thousands of years. Its nutritional value has long been recognized, as it contains various health-promoting bioactive components. Jujube polysaccharides are one of the major bioactive constituents. Extensive studies have shown that jujube polysaccharides exert multiple biological activities, such as antioxidant, anti-inflammatory, anti-tumor, immune regulatory, anti-fatigue, liver- protective, blood sugar-lowering, and blood lipid-lowering effects, through different or synergistic mechanisms. This article provides an overview of the physicochemical properties and structure-activity relationship of jujube polysaccharides, and summarizes the research progress on the bioactivity and mechanisms of jujube polysaccharides, both domestically and internationally in recent years. Based on these findings, the therapeutic potential of jujube polysaccharides for various diseases is discussed, aiming to provide references for further research and the development of related medicinal treatments involving jujube polysaccharides. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science 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.)

BACKGROUND: In pesticide research, bleaching herbicides have always been a hot topic. Our previous research showed that N‐(4‐fluorobenzyl)‐2‐methoxybenzamide is an innovative lead compound for bleaching herbicides. RESULTS: A total of 40 derivatives of picolinamides were prepared and evaluated for their herbicidal activity by Petri dish tests and postemergence trials. The structure–activity relationship (SAR) revealed that introducing electron‐withdrawing groups at the 3‐ or 4‐positions of the benzyl significantly enhances herbicidal activity. Furthermore, ZI‐04 induced similar symptoms such as bleaching effect in treated weeds and accumulation of biosynthetic precursors for carotenoids as observed with diflufenican. ZI‐04 also exhibited significant cross‐resistance to diflufenican and had a lower resistance risk than diflufenican. CONCLUSION: N‐benzyl‐6‐methylpicolinamides were discovered as a novel scaffold for bleaching herbicides. The accumulation of phytoene, phytofluene and ζ‐Carotene in radish cotyledons, and cross‐resistance observed with diflufenican, showed that title compounds can interfere with carotenoid biosynthesis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

To ensure ongoing sustainability, the modern agrochemical industry is faced with enormous challenges. These arise from provision of high‐quality food to increasing water use and environmental impact as well as a growing world population. The loss of previous agrochemicals due to consumer perception, changing grower needs and ever‐changing regulatory requirements is higher than the number of active ingredients that are being introduced into the crop protection market. Therefore, the development of novel agrochemicals is essential to provide improved efficacy and environmental profiles. In this context, the introduction of fluorine atoms and fluorine‐containing motifs into a molecule is an important method to influence its physicochemical properties. These include, for example, small difluoro‐ and trifluoromethyl, or trifluoromethoxy groups at aryl or heterocyclic aryl moieties but also fragments like 2,2,2‐trifluoroethoxycarbonyl, trifluoromethylsulfonyl, trifluoroacetyl, as well as the so far unusal rest like heptafluoro‐iso‐propyl. This review gives an overview of recent developments of fluorine‐containing pesticides launched over the past 7 years and describes a selection of current fluorine‐containing development candidates. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study highlights the biological efficiency of pyrimido[4,5‐b]quinolines as inhibitors of cancer cell growth and antioxidants and anti‐inflammatory properties, etc. Recent research studies have revealed their promising biological activity to inhibit the growth of many disease‐causing yeasts, fungi, and bacteria. The structural composition greatly affects the biological effectiveness, as these compounds exceed the value of some standard compounds against pathogenic microbes. The antioxidant potential of these derivatives is also explored. Several glycosylated and non‐glycosylated derivatives exhibited potent free radical scavenging activity and protected against DNA damage, exceeding reference standards in some cases. Furthermore, the review examines the anti‐inflammatory and analgesic properties of pyrimidoquinoline derivatives. Studies suggest their efficacy is comparable to known drugs like diclofenac and aspirin in carrageenan‐induced paw edema and hot plate tests. Pyrimidoquinoline derivatives also demonstrate promising anticancer activity. While some have minimal effects, others exhibit notable activity against various human cancer cell lines. This review documents over two decades of research, covering the period from 2000 to 2024. Overall, pyrimidoquinoline derivatives signify an auspicious class of compounds with therapeutic potential across various areas. Further research is necessary to elucidate their mechanisms of action, optimize their efficacy and selectivity, and assess their safety profiles for clinical development. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) are a significant source of environmental pollution, posing threats to human safety. With growing concerns about environmental degradation, catalytic oxidation technology emerges as a paramount and widely adopted approach for VOC elimination, renowned for its operational simplicity, energy efficiency, and environmental friendliness. As a representative transition metal catalyst, cobalt‐based catalysts have garnered widespread use in VOC catalytic oxidation due to their cost‐effectiveness, versatility, and distinctive physicochemical properties. This paper provides a detailed exposition of the construction strategies and structure‐activity relationship of Co3O4‐based catalysts in VOCs oxidation reaction, encompassing both monometallic Co3O4 and multimetallic cobalt‐based catalysts. Furthermore, it offers a comprehensive summary and discussion of the latest research progress concerning Co3O4‐based catalysts in practical applications. Concluding with a meticulous analysis, the paper addresses the technical challenges inherent in developing Co3O4‐based catalysts for VOCs degradation. Additionally, it proposes research directions aimed at overcoming these challenges, contributing to the ongoing discourse on environmental sustainability. [ABSTRACT FROM AUTHOR]

Imidazolidinone derivatives have emerged as promising anticancer agents, captivating the attention of researchers in medicinal chemistry. Imidazolidinones, characterized by their unique chemical structure, have demonstrated versatility in synthetic methodologies. Researchers have developed a variety of derivatives, each with distinct modifications, allowing for fine‐tuning of pharmacological properties. This review explores the journey of imidazolidinone compounds, from synthesis to structure‐activity exploration, and investigates their anticancer mechanistic pathways. The synthesis methodologies, including diverse approaches and reaction conditions, were examined. Structural modifications are discussed, showing the versatility sof imidazolidinone scaffolds. Mechanistic insights into their anticancer mechanisms, in vitro, ex‐vivo and in vivo activities, with their challenges in development are critically analyzed. This paper concludes by emphasizing the potential of imidazolidinone derivatives and suggesting future research directions in the pursuit of novel and effective anticancer therapeutics. [ABSTRACT FROM AUTHOR]

BACKGROUND: Frog active peptides have rich activities, such as antibacterial and anti-tumor, and are expected to solve the problem of antibiotic resistance. OBJECTIVE: The active peptide QUB2984 was discovered in the skin secretions of Agalychnis callidryas. Its structure and properties were simulated by bioinformatics. The peptide was synthesized, purified, and identified and its biological functions were investigated. METHODS: Agalychnis callidryas skin secretions were collected by electrostimulation. The sequence of QUB2984 was obtained through constructing a cDNA library with isolated mRNA. BLAST was used for peptide sequence alignment. Besides that, Iterative Threading ASSEmbly Refinement (I-TASSER) and HeliQuest tools were used for protein secondary structure simulation. It was synthesized by solid-phase peptide synthesis, purified by reverse-phase high-performance liquid chromatography, and structurally confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The purified peptide was used to evaluate its biological activity. Its antibacterial effect was evaluated by the minimum inhibitory concentration method. Its cytotoxic effect was detected by MTT assay. Its safety was investigated by a hemolysis test. RESULTS AND CONCLUSION: (1) Peptide QUB2984 had basically α-spiral structure, with a relatively intact hydrophobic surface, and a certain destructive ability to biofilm. The third amino acid position of QUB2984 was composed of W and had a G-X-G structure. (2) The minimum inhibitory concentration of QUB2984 against gram-positive Staphylococcus aureus was 2 μmol/L, the minimum inhibitory concentration against gram-negative Escherichia coli was 2 μmol/L, and the minimum inhibitory concentration against the fungus Candida albicans was 8 μmol/L. (3) The active peptide QUB2984 had obvious inhibitory effect on human non-small cell lung cancer cells NCI-H838 at 10-5 mol/L concentration, and the hemolytic effect on horse red cells at 64 μmol/L concentration was 50%. (4) The results showed that QUB2984 had anti-bacterial and anti-cancer activity, and it had a positive charge of +3, which was conducive to contact with bacteria or cells. [ABSTRACT FROM AUTHOR]

Ca doping is an effective method for improving the adsorption capacity of HA–Fe aggregates and regulating their structures. Understanding the structural characteristics of Ca–HA–Fe aggregates can help explore their microscopic adsorption effect on heavy metals. However, the heterogeneity of HA results in an incomplete understanding of the structural characteristics of the ternary system of Ca–HA–Fe aggregates and adsorption of the quaternary system of Ca–HA–Fe–Pb/Cu/Cd. In this study, interactions between Ca–HA–Fe ternary and Ca–HA–Fe–Pb/Cu/Cd quaternary systems were discussed from a molecular perspective. The structures of the basic structural units of HA were identified. Density functional theory (DFT) was employed to calculate the stable states of basic structural units of HA and Ca2+. The results showed that hydroxyl and carboxyl groups exhibited the highest capacity to bind with Ca2+. The interactions among Ca, HA, and Fe led to the formation of network aggregates. The binding energies of functional groups for heavy metals and the feasibility of ion exchange were calculated by the method of experiment and DFT. According to the contribution of functional group complexation and ion exchange, the ion exchange values for Pb2+, Cu2+, and Cd2+ were 66.71%, 62.87%, and 60.79%, respectively, which indicated that Ca2+ ion exchange showed considerable potential in enhancing the adsorption capacity of heavy metals. [ABSTRACT FROM AUTHOR]

Mineral oils and synthetic and natural esters are the predominant insulating liquids in electrical equipment. Structure–activity relationship models to predict the key properties of pure insulating liquids, including pulse breakdown strengths, AC breakdown voltages, dielectric constants, flash points, and kinematic viscosities, have been proposed for the first time. Dependence of the specific properties on the molecular structures has been illustrated quantitatively in terms of surface area, statistical total variance, and average deviation of positive and negative electrostatic potentials, as augmented by molecular weight, volume, and ovality. Moreover, the individual contribution of the functional groups to viscosity has been revealed by an additive approach. The predicted properties are in good agreement with the experimental data. The present theoretical work provides new insights on the development of novel dielectric fluids. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery. [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 versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six‐membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure–activity relationship concerning different biological activities of various piperazine‐containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines. [ABSTRACT FROM AUTHOR]

A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs. [ABSTRACT FROM AUTHOR]

Regarding the importance of thiol-thione tautomer structure and the existence of hydrogen bonding in thione tautomer structure and its effect on geometric, physicochemical, and biological properties, mono-cyclopentyl-substituted bismuthiol was synthesized via a telescopic process in a green medium. The pure product was characterized by physical and spectroscopic techniques. The suitable crystals for single crystal study were obtained after trying different solvents and mixed solvents, and long clear needle-like crystals could be isolated from a mixture of n-hexane and ethyl acetate (volume ratio of 8:2). The FTIR spectra of bismuthiol, 2,5-bis-cyclopentylsulfanyl-[1,3,4]thiadiazole, and 5-cyclopentylsulfanyl-3H-[1,3,4]thiadiazole-2-thione were studied to define the characteristic wavenumbers of thiol and thione structures. A possible hyper-conjugative interaction between the S–H and π bond of C=N, the existence of C=S and C–N–H. and stability of thione structure was demonstrated for the new product, which supports our prediction of thione or thiol structure using the study of IR spectra. Furthermore, the influence of change in 1,3,4-thiadiazol ring and the presence N–H functional group of thione structure on the transition phases and thermal stability of bismuthiol, bis-cyclopentyl-substituted, and mono-cyclopentyl-substituted bismuthiol were investigated using TGA/DTA and DSC profile analysis. The SwissADME tool was employed to predict the biocheminformatic information of bismuthiol, bis- and mono-cyclopentyl-substituted bismuthiols, which displayed high potential of all 1,3,4-thiadizole derivatives in pharmaceutical and medicine areas. Finally, an in vitro antibacterial activity of the mono- and bis-cyclopentyl substituted bismuthiol against the gram-negative (Escherichia coli ATCC 25922) and gram-positive (Staphylococcus aureus ATCC 25923) bacterial species was conducted by the disk diffusion method with cefazolin as a blank antibiotic. The results showed superior antibacterial efficiency of both derivatives. [ABSTRACT FROM AUTHOR]

Summary: Obesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti‐inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure–activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in‐depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain's substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson's disease may be happened because of various genetic and environmental factors. Parkinson's disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al. reported MAO-B inhibitors with IC50 0.0051 µM and showed good binding affinity. Enriquez et al. reported a compound with IC50 144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure–activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents. [ABSTRACT FROM AUTHOR]