Insights into the structural requirements of triazole derivatives as promising DPP IV inhibitors: computational investigations

Abstract

Diabetes is one of the leading causes of death globally as per World Health Organization 2019. To cope up with side effects of current diabetes therapy, researchers have found several novel targets for the treatment of diabetes. Currently, dipeptidyl peptidase IV (DPP IV) has emerged as a target in modulating the diabetes physiology. In the present work, various 3D-Quantitative structure activity relationship (QSAR) techniques namely comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis, topomer CoMFA and molecular hologram QSAR are used to explore the structural requirements of triazole derivatives as DPP IV inhibitors. Different models generated by 3D QSAR studies had acceptable statistical values for further prediction of molecules. From the contour maps of QSAR results, important structural features are deduced. Substitutions on N₁ and N₂ of triazole ring with H-bond donor group enhances the biological activity. Aliphatic side chain, less bulky group, H-bond donor group and –COOH group on N₃ of triazole ring are vital for the DPP IV inhibition. Moreover, electron withdrawing side chain on the triazole ring improves the biological activity. Further, novel triazole derivatives were designed and docking results of these compounds proved the efficiency of the developed 3D QSAR model. In future, results of this study may provide promising DPP IV inhibitors for the treatment of diabetes.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• DPP IV
• triazole derivatives
• 3D QSAR
• CoMFA
• CoMSIA
• topomer CoMFA
• HQSAR

Acknowledgements

We would like to thank K. B. Institute of Pharmaceutical Education and Research & L.J. Institute of Pharmacy for their research support. B. M. Shah would like to thank K. B. Institute of Pharmaceutical Education and Research for registration as research scholar.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

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