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 alpha-glycosidase inhibitors.N-Substituted pyrimidinethione and acetophenone derivatives (A1-A5,B1-B11, andC1-C11) were good inhibitors of the alpha-glycosidase enzyme, withK(i)values in the range of 104.27 +/- 15.75 to 1,004.25 +/- 100.43 nM. Among them, compoundB7was recorded as the best inhibitor, with aK(i)of 104.27 +/- 15.75 nM against alpha-glycosidase. In silico studies were carried out to clarify the binding affinity and interaction mode of the compounds with the best inhibition score against alpha-glycosidase fromSaccharomyces cerevisiae. CompoundsB7(S) andB11(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 inS. cerevisiaeand human alpha-glycosidase inhibition.