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 Ki values in the...

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Published in:	Archiv der Pharmazie (Weinheim) Vol. 353; no. 9; pp. e2000075 - n/a
Main Authors:	Taslimi, Parham, Sujayev, Afsun, Karaman, Muhammet, Maharramova, Gunel, Sadeghian, Nastaran, Osmanova, Sabiya, Sardarova, Sabira, Majdi, Nargiz, Ozel, Handan U., Gulcin, İlhami
Format:	Journal Article
Language:	English
Published:	Frankfurt Wiley Subscription Services, Inc 01-09-2020
Subjects:	acetophenone diabetes mellitus molecular docking N‐substituted pyrimidinethione α‐glycosidase
Online Access:	Get full text
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Summary:	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 Ki 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 Ki 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. 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 Ki 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0365-6233 1521-4184
DOI:	10.1002/ardp.202000075