<i>N</i>‐Substituted pyrimidinethione and acetophenone derivatives as a new therapeutic approach in diabetes
Parham Taslımı, Afsun Sujayev, Muhammet Karaman, Gunel Maharramova, Nastaran Sadeghian, Sabiya Osmanova, Sabira Sardarova, Nargiz Majdi, Handan Ucun Özel, İlhami Gülçın
Abstract
Abstract 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.