An Insilico Appraisal of Few Bioactive Compounds against Beta Keto Acyl ACP Synthase III for Antitubercular Efficacy

According to data of the World Health Organization, Tuberculosis (TB) caused by Mycobacterium tuberculosis, is considered to be the most chronic communicable disease in the World especially in Asia and Africa. This situation was made worse by the emergence of multi drug resistant TB (MDR-TB) and the increasing number of HIV-positive TB cases. Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. A series of pyrazolone linked with isonicotinic acid hydrazide were computationally designed and energy minimized. The molecular properties were calculated from suitable computational tools. 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 FabH, (PDB code-1HZP) using Argus lab docking software which showed good binding energy for the enzyme, when compared with the binding energies of standard drug isoniazid -6.17kcal/mol.) Among all the designed ligands, the ligand II and V showed more binding energy values (−8.68 and -8.86Kcal/mol) and the designed ligand are synthesized and evaluvate the TB activity by using alamar blue assay method. From the research work we found that pyrazolone linked with isonicotinic acid hydrazidehave significant role in the anti tubercular activity. The invitroactivity also suggest that the derivativesobtained from the presence of nitro (ligand II) and amino group (ligand v) in the substituted acid having appreciableactivity.