New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.

Abstract

In order to select new drugs and to predict their in vitro activity against Mycobacterium avium complex (MAC), new quantitative structure-activity relationship (QSAR) models were developed. The activities against MAC of 29 structurally heterogeneous drugs were examined by means of linear discriminant analysis (LDA) and multilinear regression analysis (MLRA) by using topological indices (TI) as structural descriptors. In vitro antimycobacterial activities were determined by a broth microdilution method with 7H9 medium. The topological model obtained successfully classifies over 80% of compounds as active or inactive; consequently, it was applied in the search for new molecules active against MAC. From among the selected candidates demonstrating in vitro activity, aflatoxin B1, benzalkonium chloride and pentamidine stand out, with MIC50s between 4 and 32 mg/L. The method described in this work is able to select molecules active against MAC.