Docking analysis of substituted pyrazoles as M. tuberculosis Enoyl ACP reductase inhibitors

Tuberculosis continues to be a major cause of morbidity and mortality all over the world. No new drug has been developed in the past 30 yr. Consequently, there is an urgent need to identify new drug targets in mycobacteria and eventually, develop new drugs. The enoyl acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. A series of pyrazoles linked with imidazoles were computationally designed and energy minimized. These ligands were investigated for drug like properties by calculating Lipinski’s rule of five using molinspiration. These compounds were docked into the active site of ENR (PDB code, 2H7I) using Argus lab docking software which showed good affinity for the enzyme, when compared with the binging energies of standard drug isoniazid (-8.39kcal/mol.) Among all the designed ligands, the ligand 4 showed more binding energy values (-10.17kcal/mol). Further we planned to synthesise these derivatives and to screen for their anti mycobacterial activity.

Author(s): Purnima. S., Subashini. S., Subhashini. N. and Solairaj. P

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