N‐Substituted pyrimidinethione and acetophenone derivatives as a new therapeutic approach in diabetes. Issue 9 (14th June 2020)

• Record Type: Journal Article
• Authors: Taslimi, Parham; Sujayev, Afsun; Karaman, Muhammet; Maharramova, Gunel; Sadeghian, Nastaran; Osmanova, Sabiya; Sardarova, Sabira; Majdi, Nargiz; Ozel, Handan U.; Gulcin, İlhami
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 9(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-06-14
• Subjects: acetophenone -- diabetes mellitus -- molecular docking -- N‐substituted pyrimidinethione -- α‐glycosidase; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000075
• Languages: English
• ISSNs: 0365-6233

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. Abstract : Compounds with 4‐hydroxybutyl, 4‐phenyl, 5‐carboxylate, and pyrimidine moieties were assayed for their activity as α‐glycosidase inhibitors. N ‐Substituted pyrimidinethione and acetophenone derivatives were identified as good inhibitors, with K i values in the range of 104.27 ± 15.75 to 1, 004.25 ± 100.43 nM. Docking results confirmed that the 4‐hydroxybutyl and pyrimidinethione moieties play a key role in the inhibition of S. cerevisiae and human α‐glycosidase.