QSAR tool for optimization of nitrobenzamide pharmacophore for antitubercular activity

Tuberculosis (TB) is a leading cause of death worldwide from a single infectious agent, Mycobacterium tuberculosis (MTB), especially due to the development of resistant strains and its co-infections in HIV. Quantitative-structure activity relationship (QSAR) studies aid rapid drug discovery. In this work, 2D and 3D QSAR studies were carried out on a series of nitrobenzamide derivatives to design newer analogues for antitubercular activity. 2D QSAR was performed using MLR on a data set showing antitubercular activity. The 3D-QSAR studies were performed by kNN–MFA using simulated annealing variable selection method. Alignment of given set of molecules was carried out by the template-based alignment method and then was used to build the 3D-QSAR model. Robustness and predictive ability of the models were evaluated by using various traditional validating parameters. Different physiochemical, alignment-based, topological, electrostatic, and steric descriptors were generated, which indicated the key structural requirements for optimizing the pharmacophore for better antitubercular activity. For 2D QSAR, the best statistical model was generated using SA-MLR method (r2 = 0.892, q2 = 0.819) while 3D QSAR model was derived using the SA KNN method (q2 = 0.722). The positively contributing descriptors can be incorporated to design new chemical entities for future study.