Novel vanillic acid derivatives containing a thiosemicarbazide moiety: As potential antioxidants and α-glucosidase inhibitors

作者：Pei Li, Dan Wang, Xiang Wang · 发表于：Phosphorus, sulfur, and silicon and the related elements · 年份：2025 · DOI：10.1080/10426507.2025.2603997 · 被引用次数：3 · 研究领域：Genomics, phytochemicals, and oxidative stress、Free Radicals and Antioxidants、Biochemical and biochemical processes

In this study, a series of novel vanillic acid derivatives incorporating a thiosemicarbazide moiety were synthesized and their structures were fully characterized by 1H NMR,13C NMR, and HRMS. Bioassay results revealed that several target compounds demonstrated significant antioxidant and α-glucosidase inhibitory activities. Notably, compound 2-(4-(benzyloxy)-3-methoxybenzoyl)-N-isopropylhydrazine-1-carbothioamide (5d) exhibited excellent DPPH and ABTS radical scavenging activity as well as α-glucosidase inhibitory activity, with the IC50 values of 5.33, 8.54, and 34.99 μg/mL, respectively, which were lower than those of vitamin C, trolox, and acarbose. Furthermore, molecular docking results revealed that compound 5d established intermolecular interactions—such as van der Waals, attractive charge, conventional hydrogen bond, carbon hydrogen bond, π-sigma, π-sulfur, and π-π stacked—with the active site of the NADPH oxidase (PDB ID: 2CDU), whereas compound 5d exhibited a broader range of interactions with the active site of yeast isomaltase (PDB ID: 3A4A), including van der Waals, attractive charge, conventional hydrogen bond, carbon hydrogen bond, π-cation, π-anion, π-π T-shaped, and π-alkyl interactions. ADMET and drug-likeness analysis results showed that compound 5d is safety and possess favorable physicochemical properties suitable for potential drug candidates. To the best of our knowledge, this is the first report on the synthesis and bioactivity evaluation of this series...