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

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 IC<sub>50</sub> 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.

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Publication Details

Journal
Scientific Reports
Published
2024-11-11
DOI
https://doi.org/10.1038/s41598-024-78878-2
Citations
11
Primary Topic
Quinazolinone synthesis and applications
Type
article
Field-Weighted Citation Impact
2.75

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article

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

Alireza Foroumadi, Somayeh Mojtabavi, Maliheh Barazandeh Tehrani, Loghman Firoozpour et al.
11 citations
Scientific Reports
Quinazolinone synthesis and applications
2.75
article

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

Alireza Foroumadi, Somayeh Mojtabavi, Maliheh Barazandeh Tehrani, Loghman Firoozpour, Mohammad Ali Faramarzi, Roham Foroumadi, Fariba Peytam, Maryam Norouzbahari, Faezeh Sadat Hosseini, Bahareh Bayati, Fahimeh Bonyasi, Mahdis Sadeghi Moghadam, Ruzbehan Divsalar, Reza Fathimolladehi, Mohammad Javad Dehghan Nayeri
article en
11 citations

Abstract

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 IC<sub>50</sub> 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.

Scientific ReportsVol. 14(1)
Kerman University of Medical Sciences (IR), University of Tabriz (IR), Final International University (CY), Tehran University of Medical Sciences (IR)
Tehran University of Medical Sciences and Health Services
Openalex Percentile: Top 9%
Quinazolinone synthesis and applications
2.75
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