Synthesis, In Vitro α-Amylase Activity, and Molecular DockingStudy of New Benzimidazole Derivatives
Hayat Ullah, Hafeez Ullah, Muhammad Taha, Fahad Khan, Fazal Rahim, Imad Uddin, Muhammad Sarfraz, Syed Adnan Alı Shah, Aamir Aziz, Sidra Mubeen
Abstract
New benzimidazole derivatives were synthesized by reacting substituted phenacyl bromides with 1H-benzimidazole-2-thiols. The synthesized compounds were characterized through 1H and 13C NMR and high-resolution mass spectra. Their evaluation for α-amylase activity revealed inhibitory potential with IC50 values ranging from 1.20±0.05 to 19.10±0.30 μM against IC50 = 1.70±0.10 μM for the standard drug acarbose. Among the examined series, 2-[(1H-benzimidazole-2-yl)sulfanyl]-1-(3–nitrophenyl)ethan-1-one (IC50 = 1.20±0.05 µM) was the most potent. Other nitro-substituted analogs showed good potency with IC50 values of 2.10±0.10, 2.20±0.10 and 2.10±0.10 µM. Limited structure–activity relationship was established for all derivatives based on the nature, position, and number of substituents on the aryl ring. Binding sites of the most active compounds were determined by the molecular docking study.