Design, synthesis, and evaluation of novel substituted imidazo[1,2-c]quinazoline derivatives as potential α-glucosidase inhibitors with bioactivity and molecular docking insights

被引:1
作者
Peytam, Fariba [1 ]
Hosseini, Faezeh Sadat [1 ]
Fathimolladehi, Reza [2 ]
Nayeri, Mohammad Javad Dehghan [3 ]
Moghadam, Mahdis Sadeghi [1 ]
Bayati, Bahareh [1 ]
Norouzbahari, Maryam [4 ]
Foroumadi, Roham [5 ]
Bonyasi, Fahimeh [2 ]
Divsalar, Ruzbehan [6 ]
Mojtabavi, Somayeh [7 ]
Faramarzi, Mohammad Ali [7 ]
Tehrani, Maliheh Barazandeh [2 ]
Firoozpour, Loghman [1 ,2 ]
Foroumadi, Alireza [1 ,6 ]
机构
[1] Univ Tehran Med Sci, Inst Pharmaceut Sci TIPS, Drug Design & Dev Res Ctr, Tehran, Iran
[2] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran
[3] Univ Tabriz, Fac Nat Sci, Dept Biol, Tabriz 5166616471, Iran
[4] Final Int Univ, Fac Pharm, Via Mersin 10, Kyrenia, Cyprus
[5] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran
[6] Kerman Univ Med Sci, Inst Neuropharmacol, Neurosci Res Ctr, Kerman, Iran
[7] Univ Tehran Med Sci, Fac Pharm, Dept Pharmaceut Biotechnol, Tehran, Iran
来源
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
关键词
Diabetes; <italic>alpha</italic>-Glucosidase; Imidazo[1,2-<italic>c</italic>]quinazoline; Imidazoquinazoline; EFFICIENT SYNTHESIS; DUAL INHIBITORS; CLICK CHEMISTRY; BENZIMIDAZOLES; MECHANISMS; HYBRIDS; UREASE; AGENTS;
D O I
10.1038/s41598-024-78878-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
alpha-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 alpha-glucosidase, revealing IC50 values ranging from 50.0 +/- 0.12 mu M to 268.25 +/- 0.09 mu M. 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.
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页数:23
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