Synthesis, biological evaluation and molecular docking study of benzimidazole derivatives as α-glucosidase inhibitors and anti-diabetes candidates

• Published in: Journal of Molecular Structure
• Main Author: Hayat S.; Ullah H.; Rahim F.; Ullah I.; Taha M.; Iqbal N.; Khan F.; Khan M.S.; Shah S.A.A.; Wadood A.; Sajid M.; Abdalla A.N.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85144315169&doi=10.1016%2fj.molstruc.2022.134774&partnerID=40&md5=2a72a14232bed211839dccaa449b79b9

Voglibose and acarbose are distinguished α-glucosidase inhibitors used for controlling diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still a need to develop safer therapy. Despite a broad spectrum of the biological importance of benzimidazole, it is occasionally evaluated for α-glucosidase activity. The current study deals with the synthesis and biological screening of benzimidazole derivatives (1-17) for their α-glucosidase inhibitory activity. All derivatives showed an excellent to good inhibitory potential with IC50values 3.40 ± 0.10 to 36.90 ± 0.90 μM as compared to standard drug acarbose (IC50 =38.60 ± 0.20 μM). Among the series, derivative 17 was the most potent one with IC50 value 3.40 ±0.10 μM and all other derivatives 11,10, 12, 4, 8, 3, 15, 9, 14, 2, 5, 13, 6, 16 and 1 showedIC50 values 5.10 ± 0.20, 6.2 ± 0.20, 9.30 ± 0.30, 16.50 ± 0.40, 16.80 ± 0.40, 17.20 ± 0.40, 17.30 ± 0.30, 20.90 ± 0.50, 24.70 ± 0.6,25.50 ± 0.50, 27.40 ± 0.60, 28.60 ± 0.60, 28.80 ± 0.60, 32.40 ± 0.70 and36.50 ± 0.90 μM respectively which were many fold better as compare to standard drug. The structure-activity relationship was established and binding interactions were confirmed through molecular docking studies. © 2022 Elsevier B.V.