Pei Li

In this work, a series of novel thiochroman‐4‐one derivatives incorporating a thiosemicarbazide moiety were rationally designed and synthesized. In vitro bioactivity assays demonstrated that most target compounds exerted potent ABTS radical scavenging and α‐glucosidase inhibitory activities. Notably, compound 6m exhibited superior bioactivities, with an IC ₅₀ value of 12.96 µM for ABTS radical scavenging and 27.48 µM for α‐glucosidase inhibition, which were markedly stronger than those of the positive controls Trolox and acarbose, respectively. Molecular docking and 100 ns molecular dynamics (MD) simulation results suggested that compound 6m may form plausible and stable non‑covalent interactions with the active sites of human peroxiredoxin 5 (PDB ID: 4K7N) and human α‑glucosidase (PDB ID: 3TOP). In silico druggability and ADMET evaluations suggested that compound 6m might possess favorable physicochemical properties and biosafety profiles; these computational predictions remain to be validated by further biological experiments. In addition, compound 6k showed the highest antibacterial potency, with EC ₅₀ values of 39.37 µM against Xoo and 49.21 µM against Xac , which were higher than bismerthiazol and thiodiazole copper.

In this study, a series of novel vanillic acid semicarbazide hybrids were successfully synthesized and structurally characterized via ¹H, ¹³C NMR, and HRMS. The in vitro antioxidant potential of all target compounds was systematically assessed by DPPH and ABTS radical scavenging assays. Biological screening results demonstrated that compound 2-(4-hydroxy-3-methoxybenzoyl)-N-isopropylhydrazine-1-carboxamide exhibited in vitro outstanding radical scavenging potency with the half-maximal inhibitory concentration (IC₅₀) values of 4.7 and 0.2 μg/mL toward DPPH and ABTS radicals, respectively, which were remarkably lower than those of vanillic acid, vitamin C and trolox. Meanwhile, molecular docking simulations further revealed that compound 2-(4-hydroxy-3-methoxybenzoyl)-N-isopropylhydrazine-1-carboxamide could form multiple stable interactions with the active pocket of human peroxiredoxin 5 (PDB entry: 4K7N), which rationally explained its potent antioxidant activity at the molecular level. Moreover, in silico ADMET and drug-likeness evaluations indicated that compound 2-(4-hydroxy-3-methoxybenzoyl)-N-isopropylhydrazine-1-carboxamide possessed favorable physicochemical profiles, acceptable oral bioavailability and negligible toxic risks, highlighting its great potential as a lead antioxidant candidate for further pharmaceutical development.

Herein, a series of novel thiochroman‐4‐one derivatives bearing sulfonyl hydrazone moiety were rationally designed and synthesized via molecular hybridization strategy. The sulfonyl hydrazone pharmacophore with excellent hydrogen‐bonding interaction ability was first introduced into the thiochroman‐4‐one parent skeleton to construct dual‐active functional molecules, aiming to achieve synergistic α‐glucosidase inhibition and antioxidant activity for antidiabetic therapy. All target compounds were structurally characterized by ¹ H NMR, ^{1 3} C NMR, and HRMS. Bioactivity results showed that multiple derivatives exhibited excellent α‐glucosidase inhibitory activity and antioxidant capacity, among which compound 5k displayed the optimal comprehensive pharmacological performance with IC ₅₀ value of 4.57 µg/mL against α‐glucosidase, which was significantly superior to the positive control acarbose (237.48 µg/mL). Molecular docking and molecular dynamics (MD) simulation verified that the optimal compound 5k could stably bind to the active pocket of α‐glucosidase through multiple hydrogen bonds and hydrophobic interactions, with lower binding energy and better complex stability. Drug‐likeness evaluation demonstrated that all synthesized derivatives complied with Lipinski's rule of five and had favorable pharmacokinetic properties. This work provides a novel structural scaffold for the development of high‐efficiency antioxidant, α‐glucosidase, and antibacterial inhibitors, and demonstrates its potential as a lead compound for pharmaceutical and agrochemical development.

1. In recent years, scientific attention has increasingly shifted toward preventive healthcare, particularly focusing on the impact of reactive oxygen species (ROS).[1] The interdisciplinary study ...

Pichia manshurica (P. manshurica), a gas-producing spoilage yeast prevalent in fermented foods, causes package swelling, off-flavor formation, and quality deterioration, thereby shortening shelf life and reducing commercial value. Carvacrol, a natural phenolic compound from plant essential oils, has broad-spectrum antimicrobial activity, but its mechanism for inhibiting P. manshurica’s gas production is unclear. In this study, in vitro and in situ experiments confirmed that carvacrol significantly inhibits gas production by P. manshurica in a concentration-dependent manner. Transcriptomic analysis identified 374 differentially expressed genes (DEGs), which were mainly enriched in biological processes such as nitrogen compound metabolism, lipid metabolism, and organic substance biosynthesis, as well as cellular components including the cell membrane, mitochondrion, and endoplasmic reticulum. Metabolomic analysis screened a total of 440 differentially accumulated metabolites (DAMs), primarily involving carboxylic acids, phospholipids, fatty acids, and amino acids. Integrated transcriptome–metabolome analysis revealed that carvacrol disrupts cell membrane integrity, blocks the tricarboxylic acid cycle and oxidative phosphorylation, and interferes with energy, lipid, and amino acid metabolism in P. manshurica, thereby suppressing its gas production. This study elucidates the molecular mechanism by which carvacrol inhibits gas production by P. manshurica, providing a theoretical basis for the development and application of carvacrol as a natural preservative in fermented foods.

In this study, a series of pyrimidine derivatives incorporating a thiosemicarbazide functional group were synthesized, and their structures were thoroughly characterized using ¹ H NMR, ¹³ C NMR, and HRMS. Biological assays demonstrate that compound 5a exhibits exceptional in vitro antioxidant activity, with IC ₅₀ values of 3.96 µg/mL for DPPH radical scavenging and 2.01 µg/mL for ABTS radical scavenging, both of which are lower than those of the reference standards vitamin C (6.38 µg/mL) and trolox (8.04 µg/mL). Compound 5k shows significant in vitro α‐glucosidase inhibitory activity, achieving an IC ₅₀ value of 38.62 µg/mL, which is markedly lower than that of acarbose (237.48 µg/mL). Meanwhile, molecular docking results reveal that compounds 5a and 5k establish strong binding affinity to intermolecular interactions with the active site of the NADPH oxidase (PDB ID: 2CDU) and human intestinal α‐glucosidase (PDB: 3TOP), respectively. Furthermore, molecular dynamics (MD) simulations indicate that compounds 5a and 5k forms stable interaction with the NADPH oxidase and human intestinal α‐glucosidase, primarily driven by van der Waals forces. In addition, ADMET and drug‐likeness analysis results show that the compound 5k is safety and possess favorable physicochemical properties suitable for potential drug candidate.

In this study, using the plant-derived active compounds guaiacol and carvacrol as the lead structures, a series of novel phenol derivatives bearing an 1,2,4-triazole thioether scaffold were synthesized, and their structures were characterized by ¹H, ¹³C NMR, and HRMS. The in vitro antioxidant and α-glucosidase inhibitory activities of these compounds were subsequently evaluated. Bioassay results demonstrated that the target compounds exhibited certain in vitro DPPH and ABTS scavenging as well as α-glucosidase inhibitory activities. Notably, 4-ethyl-3-[(5-isopropyl-2-methylphenoxy)methyl]-5-(propylthio)-4H-1,2,4-triazole displayed excellent in vitro α-glucosidase inhibitory activity, with an inhibition rate of 56.68%, surpassing that of the reference drug acarbose (53.00%). To the best of our knowledge, this is the first report on the synthesis and biological evaluation of this class of phenol derivatives bearing an 1,2,4-triazole thioether scaffold.