Syntheses, in vitro evaluation and molecular docking studies of 5-bromo-2-aryl benzimidazoles as α-glucosidase inhibitors

• Published in: Medicinal Chemistry Research
• Main Author: Arshad T.; Khan K.M.; Rasool N.; Salar U.; Hussain S.; Tahir T.; Ashraf M.; Wadood A.; Riaz M.; Perveen S.; Taha M.; Ismail N.H.
• Format: Article
• Language: English
• Published: Birkhauser Boston 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979210899&doi=10.1007%2fs00044-016-1614-y&partnerID=40&md5=783f7712e81dcb8af6637a6d3aa7ba17

Based on the previous reports on α-glucosidase inhibitory activity of benzimidazole class, we intend to evaluate further this class as potential inhibitors of α-glucosidase enzyme. Thus, in the current study synthesis of 5-bromo-2-aryl benzimidazole derivatives 1–25 was carried out. All the synthetic compounds were characterized by different spectroscopic techniques EIMS, HRMS, 1H-NMR, and 13C-NMR. Molecular docking was also performed on the selected compounds 1, 4, 7, and 17 having varying substitution pattern in order to understand the molecular interaction of molecules with the active site of the enzyme. All compounds were evaluated for their in vitro α-glucosidase inhibitory activities. Twenty-three compounds out of twenty-five showed excellent to moderate activity in the range of IC50 = 12.4–103.2 μM. Inhibitory results were compared with the standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 1 (IC50 = 37.82 ± 0.08 μM), 9 (IC50 = 37.76 ± 0.05 μM), 12 (IC50 = 24.96 ± 0.09 μM), 16 (IC50 = 21.15 ± 0.08 μM) and 17 (IC50 = 8.34 ± 0.02 μM) showed excellent inhibition as compared to standard drug acarbose (IC50 = 38.25 ± 0.12 μM). Especially, 17 (IC50 = 8.34 ± 0.02 μM) was found to be five-fold more active than the standard. © 2016, Springer Science+Business Media New York.