Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors

Nasli Esfahani, Anita; Iraji, Aida; Alamir, Amir; Moradi, Shahram; Asgari, Mohammad Sadegh; Hosseini, Samanesadat; Mojtabavi, Somayeh; Nasli-Esfahani, Ensieh; Faramarzi, Mohammad Ali; Bandarian, Fatemeh; Larijani, Bagher; Hamedifar, Haleh; Hajimiri, Mir Hamed; Mahdavi, Mohammad

A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC(50) values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC(50) = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-021-10310-7.