QSAR and Molecular Docking Studies on Nitro (Triazole/Imidazole)-Based Compounds as Anti-Tubercular Agents

Abstract

Tuberculosis is a chronic infectious disease which remains one of the leading causes of death worldwide. Scientists are currently engaging both experimental and theoretical methods to seek solution to this deadly disease. This work is aimed at identifying descriptors that described the anti-Mycobacterium tuberculosis H37Rv activity of nitro(triazole/imidazole)-based compounds and reliable quantitative structure activity relationship (QSAR) model were developed using selected descriptors as well as observing non-bonding interactions between studied complexes. Nineteen molecules comprising 3-nitrotriazole-and nitroimidazole-analogues were studied as anti-tubercular agents against Rv0371c from Mycobacterium tuberculosis H37Rv (PDB ID: 2we9) using semi-empirical PM3 method, quantitative structure activity relation (QSAR) studies and Docking approaches. QSAR model was successfully developed, and the studies indicated that four 2D descriptors (nO, ATS3m, ATS6m and ATS7m) were important factors for the observed biological activity. Also, the studied docking studies revealed that all the studied compounds could form a stable complex with the active site of the protein with compound 10 (N-([1,1'-biphenyl]-3-yl)-2-(3-nitro-1H-1,2,4-triazol-1-yl)acetamide) forming the most stable complex. It was observed that the obtained descriptors perfectly described the anti-Mycobacterium tuberculosis activity of the studied nitro(triazole/imidazole)-based compounds and the developed QSAR model proved to be reliable by accurately predicting the experimental IC50. Nonbonding interaction between nitro(triazole/imidazole)-based compounds and Mycobacterium tuberculosis H37Rv (PDB ID: 2we9) showed that compound 10 with-8.0 kcal/mol have higher tendency to inhibit Mycobacterium tuberculosis H37Rv (PDB ID: 2we9) than other studied compounds.