A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents

Abstract

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q ² = 0.594, r ² = 0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r ² value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.

Keywords:

• 3D-QSAR
• CoMSIA
• Indoles
• CYP51
• L. mexicana

Acknowledgments

The authors would like to thank Yang Ji Chemical Co Ltd. for their financial support of this work. We acknowledge Pr. P. Chavatte and Dr. A. Farce for their constant support and their helpful advice in realizing this project. We thank Mr. I. Nicholson for a thorough review of the manuscript.