Synthesis, In Vitro α-Amylase Activity, and Molecular Docking Study of New Benzimidazole Derivatives

• Published in: Russian journal of organic chemistry 2021-06, Vol.57 (6), p.968-975
• Main Authors: Ullah, Hayat, Ullah, Hafeez, Taha, M., Khan, F., Rahim, F., Uddin, I., Sarfraz, M., Shah, S. A. Ali, Aziz, A., Mubeen, S.
• Format: Article
• Language: English
• Subjects: Amylases; Binding sites; Bromides; Chemical synthesis; Chemistry; Chemistry and Materials Science; Mass spectra; Molecular docking; NMR; Nuclear magnetic resonance; Organic Chemistry; Substitutes; Thiols
• ISSN: 1070-4280; 1608-3393
• DOI: 10.1134/S1070428021060130

New benzimidazole derivatives were synthesized by reacting substituted phenacyl bromides with 1 H -benzimidazole-2-thiols. The synthesized compounds were characterized through 1 H and 13 C NMR and high-resolution mass spectra. Their evaluation for α-amylase activity revealed inhibitory potential with IC 50 values ranging from 1.20±0.05 to 19.10±0.30 μM against IC 50 = 1.70±0.10 μM for the standard drug acarbose. Among the examined series, 2-[(1 H -benzimidazole-2-yl)sulfanyl]-1-(3–nitrophenyl)ethan-1-one (IC 50 = 1.20±0.05 µM) was the most potent. Other nitro-substituted analogs showed good potency with IC 50 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.