N-Substituted pyrimidinethione and acetophenone derivatives as a new therapeutic approach in diabetes

In this study, compounds with 4-hydroxybutyl, 4-phenyl, 5-carboxylate, and pyrimidine moieties were determined as α-glycosidase inhibitors. N-Substituted pyrimidinethione and acetophenone derivatives (A1-A5, B1-B11, and C1-C11) were good inhibitors of the α-glycosidase enzyme, with K_i values in the range of 104.27 ± 15.75 to 1,004.25 ± 100.43 nM. Among them, compound B7 was recorded as the best inhibitor, with a K_i of 104.27 ± 15.75 nM against α-glycosidase. In silico studies were carried out to clarify the binding affinity and interaction mode of the compounds with the best inhibition score against α-glycosidase from Saccharomyces cerevisiae. Compounds B7 (S) and B11 (R) exhibited a good binding affinity with docking scores of -8.608 and 8.582 kcal/mol, respectively. The docking results also showed that the 4-hydroxybutyl and pyrimidinethione moieties play a key role in S. cerevisiae and human α-glycosidase inhibition.