Quantitative structure–activity relationship and molecular docking of 4-Alkoxy-Cinnamic analogues as anti-mycobacterium tuberculosis

Abstract

Quantitative structure–activity relationship (QSAR) and molecular docking studies were carried out on 4-Alkoxy-Cinnamic derivatives as potent anti-mycobacterium tuberculosis. Chemical structures of the molecules were optimized by employing Density Functional Theory and utilizing (B3LYP) with the 6-31G∗ basis set. Four models were generated by Genetic Function Approximation (GFA). Model one was selected as the optimum model based on validation parameters which were found to be significant with correlation coefficient (R2) of 0.980921, adjusted correlation coefficient (R2 adj) value of 0.97547 and Cross validation coefficient (Qcv2) value of 0.965244. External validations were employed to validate the chosen model and the model was found to have (R2test) of 0.8756 and Coefficient of determination for Y-randomization (c Rp2) value of 0.867578. The Molecular docking studies showed that the ligand 1,2,3,4,5 and 6 with better activities have higher bind affinities ranging from (−6.4 and −10.4 kcal/mol) which formed H-bonds and hydrophobic interactions with amino acid residues of mycobacterum tuberculosis (M. tuberculosis) DNA gyrase receptor. This research has shown that the binding affinities of these inhibitors were found to be better than the commercially sold anti-mycobacterium tuberculosis; enthambutol (−5.8 kcal/mol) and isoniazid (−5.3 kcal/mol). QSAR model generated and molecular docking results propose the direction for the design of new anti-tubercular agents with better activities against DNA gyrase.