Synthesis, characterization, X-ray, α-glucosidase inhibition and molecular docking study of new triazolic systems based on 1,5-benzodiazepine via 1,3-dipolar cycloaddition reactions

Abstract

We report in this work a synthesis of novel triazolo[1,5]benzodiazepine derivatives by the 1,3-dipolar cycloaddition reaction of N-aryl-C-ethoxycarbonylnitrilimines with 1,5-benzodiazepines. All the structures of the new compounds were determined from their NMR (¹H and ¹³C) and HRMS. Then, X-ray crystallography analysis of compound 4d confirmed the stereochemistry of cycloadducts. The compounds 1, 4a–d, 5a–d, 6c, 7 and 8 were evaluated for their in vitro anti-diabetic activity against α-glucosidase. The compounds 1, 4d, 5a and 5b showed potential inhibitory activities compared to standard acarbose. Additionally, an in silico docking study was conducted to look into the active binding mode of the synthesized compounds within the target enzyme.

Communicated by Ramaswamy H. Sarma

KEYWORDS:

• Benzodiazepines
• chemo-regioselective
• X-ray
• α-glucosidase inhibition
• molecular docking study

Acknowledgements

The authors would like to thank Professor E.M EL HADRAMI, and Professor Y. KANDRI-RODI, Faculty of Sciences and Techniques, Fez, for spectral analysis (HRMS) of the compounds. We also thank the managers of the analysis and characterization center of the Faculty of Sciences Semlalia Marrakech, Morocco, for spectral analysis (NMR) of the synthesized heterocycles.

Disclosure Statement

The authors declare that they have no known competitive financial interests or personal relationships that may have influenced the work in this article.

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Funding

The author(s) reported there is no funding associated with the work featured in this article.