Search

Design, synthesis, in vitro, and in silico enzymatic evaluations of thieno[2,3- b ]quinoline-hydrazones as novel inhibitors for α-glucosidase. [Display omitted] • Quinoline, thiophene, and hydrazone were selected as the potent pharmacophores against α-glucosidase. • Thieno[2,3- b ]quinoline-hydrazones 9 were synthesized as the new α-glucosidase inhibitors. • Compounds 9c-d , 9h , and 9l exhibited high anti-α-glucosidase activity. • Compounds 9c was a promising lead in order to achieve an anti-diabetes drug. In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3- b ]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR, 1H NMR, 13C NMR, and elemental analysis. Inhibitory activities of the title compounds were evaluated against yeast α-glucosidase. In particular, compounds 9c , 9d , and 9h exhibited high anti-α-glucosidase activity. Representatively, compound 9c with IC 50 = 1.3 µM, was 576-times more potent than positive control acarbose. Molecular docking study of the most active compounds showed that these compounds formed important binding interactions at α-glucosidase active site. Molecular dynamics study of compound 9c was also performed and the obtained results were compared with acarbose. Compounds 9c , 9d , and 9h were also evaluated for in silico druglikeness properties and ADMET prediction. These studies showed that the title most potent compounds could be exploited as drug candidates. [ABSTRACT FROM AUTHOR]