Danova A.Pattanapanyasat K.KowitShigeta Y.Rungrotmongkol T.Hermawati E.Chavasiri Hengphasatporn W.Mahidol University2024-03-072024-03-072024-03-05ChemistrySelect Vol.9 No.9 (2024)https://repository.li.mahidol.ac.th/handle/20.500.14594/97491Type 2 diabetes is common and involves α-glucosidase inhibition to regulate glucose. We synthesized twenty E-arylidene steroids with hydroxy and methoxy groups on the aromatic ring. Compounds 3 a, 5 a, 5 b, and 5 d showed notable inhibition, with IC50 values ranging from 1.84±0.28 to 9.25±2.53 μM. Key features for bioactivity include ortho methoxy and α-hydroxy. Various inhibition mechanisms were observed. In silico studies elucidate the possible binding modes of E-arylidene steroids, confirming their enzymatic mechanisms of non/un-competitive inhibitors. Allosteric site 2 emerges as a potential binding site for compounds 3 a, 5 a, and 5 b. Compound 5 d holds promise as a potent α-glucosidase inhibitor compared to acarbose at the orthosteric receptor binding site.ChemistryArticleSCOPUS10.1002/slct.2023038872-s2.0-8518623047523656549