Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors

• Published in: Bioorganic chemistry 2020-01, Vol.95, p.103482, Article 103482
• Main Authors: Asemanipoor, Nafise, Mohammadi-Khanaposhtani, Maryam, Moradi, Shahram, Vahidi, Mahbobeh, Asadi, Mehdi, Faramarzi, Mohammad Ali, Mahdavi, Mohammad, Biglar, Mahmood, Larijani, Bagher, Hamedifar, Haleh, Hajimiri, Mir Hamed
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole; alpha-Glucosidases - metabolism; Benzimidazole; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Dose-Response Relationship, Drug; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Humans; Kinetics; Molecular docking; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Triazoles - chemistry; Triazoles - pharmacology; α-Glucosidase inhibitor
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103482

A novel series of benzimidazole-1,2,3-triazole hybrids 8a-n was were synthesized by click chemistry and evaluated as potent α-glucosidase inhibitors. All the synthesized compounds showed anti-α-glucosidase activity more than standard inhibitor acarbose. [Display omitted] •A novel series of benzimidazole-1,2,3-triazole-acetamide hybrids 8a-n was synthesized and evaluated as potent α-glucosidase inhibitors.•All the title compounds showed α-glucosidase inhibition superior to standard drug acarbose.•Compound 8c with N-4-ethylphenylacetamide was the most active compound (IC50 = 25.2 ± 0.9).•This compound was a competitive inhibitor against α-glucosidase (Ki = 23 μM). In this study, a series of benzimidazole-1,2,3-triazole hybrids 8a-n as new α-glucosidase inhibitors were designed and synthesized. In vitro α-glucosidase inhibition activity results indicated that all the synthesized compounds (IC50 values ranging from 25.2 ± 0.9 to 176.5 ± 6.7 μM) exhibited more inhibitory activity in comparison to standard drug acarbose (IC50 = 750.0 ± 12.5 μM). Enzyme kinetic study on the most potent compound 8c revealed that this compound was a competitive inhibitor into α-glucosidase. Moreover, the docking study was performed in order to evaluation of interaction modes of the synthesized compounds in the active site of α-glucosidase and to explain structure-activity relationships of the most potent compounds and their corresponding analogs.