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

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 (q2 = 0.594, r2 = 0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r2 value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.