Design, synthesis, and in silico studies of quinoline-based-benzo[d]imidazole bearing different acetamide derivatives as potent α-glucosidase inhibitors

• Published in: Scientific reports Vol. 12; no. 1; p. 14019
• Main Authors: Noori, Milad, Davoodi, Ali, Iraji, Aida, Dastyafteh, Navid, Khalili, Minoo, Asadi, Mehdi, Mohammadi Khanaposhtani, Maryam, Mojtabavi, Somayeh, Dianatpour, Mehdi, Faramarzi, Mohammad Ali, Larijani, Bagher, Amanlou, Massoud, Mahdavi, Mohammad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.08.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/154/309; 631/154/309/2144; 631/92; 631/92/607; Acarbose; Design; Diabetes; Diabetes mellitus; Enzymes; Glucose; Humanities and Social Sciences; Hyperglycemia; Imidazole; Metabolism; multidisciplinary; Pharmacy; Research centers; Science; Science (multidisciplinary); α-Glucosidase
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-18455-7

In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC 50 values in the range of 3.2 ± 0.3–185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC 50  = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.