Design, synthesis, and evaluation of novel substituted imidazo1,2-cquinazoline derivatives as potential α-glucosidase inhibitors with bioactivity and molecular docking insights

• Published in: Scientific reports 2024-11, Vol.14 (1), p.27507
• Main Authors: Peytam, Fariba, Hosseini, Faezeh Sadat, Fathimolladehi, Reza, Nayeri, Mohammad Javad Dehghan, Moghadam, Mahdis Sadeghi, Bayati, Bahareh, Norouzbahari, Maryam, oumadi, Roham, Bonyasi, Fahimeh, Divsalar, Ruzbehan, Mojtabavi, Somayeh, Faramarzi, Mohammad Ali, Tehrani, Maliheh Barazandeh, Firoozpour, Loghman, oumadi, Alireza
• Format: Article
• Language: English
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-78878-2

α-Glucosidase inhibitors are important in the treatment of type 2 diabetes by regulating blood glucose levels and reducing carbohydrate absorption. The present study focuses on identifying new inhibitors bearing imidazo[1,2-c]quinazoline backbone through multi-step synthesis. The inhibitory potencies of the novel derivatives were tested against Saccharomyces cerevisiae α-glucosidase, revealing IC50 values ranging from 50.0 ± 0.12 µM to 268.25 ± 0.09 µM. Among them, 2-(4-(((2,3-diphenylimidazo[1,2-c]quinazolin-5-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (19e) and 2-(4-((benzo[4,5]imidazo[1,2-c]quinazolin-6-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (27e) emerged as the most potent inhibitors and were further investigated in various assessments. Finally, molecular docking studies were performed to reveal the crucial binding interactions and to confirm the results obtained from structure-activity relationship (SAR) analysis.α-Glucosidase inhibitors are important in the treatment of type 2 diabetes by regulating blood glucose levels and reducing carbohydrate absorption. The present study focuses on identifying new inhibitors bearing imidazo[1,2-c]quinazoline backbone through multi-step synthesis. The inhibitory potencies of the novel derivatives were tested against Saccharomyces cerevisiae α-glucosidase, revealing IC50 values ranging from 50.0 ± 0.12 µM to 268.25 ± 0.09 µM. Among them, 2-(4-(((2,3-diphenylimidazo[1,2-c]quinazolin-5-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (19e) and 2-(4-((benzo[4,5]imidazo[1,2-c]quinazolin-6-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (27e) emerged as the most potent inhibitors and were further investigated in various assessments. Finally, molecular docking studies were performed to reveal the crucial binding interactions and to confirm the results obtained from structure-activity relationship (SAR) analysis.