Design, synthesis, <i>in vitro</i>, and <i>in silico</i> studies on promising α-glucosidase inhibitors based on a quinazolinone-thiophene scaffold.

ABSTRACT: To discover novel inhibitors for α-glucosidase, a new scaffold featuring a quinazolinone-thiophene skeleton was designed through molecular hybridization. Eighteen derivatives, 14a-f, 15a-f, and 19a-f, were synthesized from this scaffold. These compounds were tested against yeast α-glucosidase. The in vitro enzymatic assays showed that all but one of the new compounds were active against α-glucosidase. The most potent compound was 19d, which inhibited the activity 11.7 times more effectively than acarbose, a standard inhibitor. In vitro kinetic studies demonstrated that this compound is a competitive inhibitor. Furthermore, in silico docking studies showed that compound 19d interacts with key residues in the active sites of both homology-modeled yeast and human α-glucos

SUBMITTER: Baghershahi P 

PROVIDER: S-EPMC12854691 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature