SMILES-based QSAR and molecular docking study of xanthone derivatives as α-glucosidase inhibitors

Abstract

Increasing diabetic population is one of the major health concerns all over the world. Inhibition of α-glucosidase is a clinically proved and attractive strategy to manage diabetes. In this study, robust and reliable QSAR models to predict α-glucosidase inhibitory potential of xanthone derivatives are developed by the Monte Carlo technique. The chemical structures are represented by SMILES notation without any 3D-optimization. The significance of the index of ideality correlation (IIC) with applicability domain (AD) is also studied in depth. The models developed using CORAL software by considering IIC criteria are found to be statistically more significant and robust than simple balance of correlation. The QSAR models are validated by both internal and external validation methods. The promoters of increase and decrease of activity are also extracted and interpreted in detail. The interpretation of developed models explains the role of different structural attributes in predicting the pIC₅₀ of xanthone derivatives as α-glucosidase inhibitors. Based on the results of model interpretation, modifications are done on some xanthone derivatives and 15 new molecules are designed. The α-glucosidase inhibitory activity of novel molecules is further supported by docking studies.

Keywords:

• Xanthone derivatives
• α-glucosidase
• QSAR
• IIC
• molecular docking

Acknowledgments

The authors would like to express their deepest gratitude to Dr. Alla P. Toropova and Dr. Andrey A. Toropov for providing the CORAL software. The authors received no financial support for the research, authorship, and/or publication of this article.

Author contributions

S.A. and A.A. conceived of the presented idea. S.A. and Z.M. developed the QSAR and performed molecular docking calculations. S.A. and A.K. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.