Atom based 3D-QSAR study of 1,4-benzodiazepine-2-ones as potent anti-trypanosomal agents and its validation

Abstract

In the investigation, a robust pharmacophore model to investigate structure–activity relationship of 1,4-benzodiazepine-2-ones derivatives was developed for human African trypanosomiasis (HAT) using PHASE module of Schrodinger software. The pharmacophore model consists of five contours such as two aromatic rings (R), one hydrophobic hydrogen (H) and two hydrogen-bond acceptor (A) with discrete geometries. The generated pharmacophore model was used to derive a predictive atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) model for the studied data set. The obtained 3D-QSAR model has an excellent correlation coefficient value (R 2 = 0.97) along with good statistical significance as shown by high Fisher ratio (F = 216.80). The model also exhibits good predictive power confirmed by the high value of cross-validated correlation coefficient (Q 2 = 0.80). To confirm the validity of the model further calculation of the enrichment factor and percentage recovery studies were calculated, which confirm the validity of the model. The findings of the QSAR study provide a set of guidelines for designing compounds with better HAT inhibitory activity.