Design, Synthesis, Characterization and Biological Evaluation of Some Novel Benzimidazole (Schiff’ Base) Derivatives as Anti-Tubercular Agents against INHA

Enoyl acyl carrier protein reductase is a vital enzyme present in the cell wall of Mycobacterium tuberculosis. • A database of 200 molecules with high prospects of inhibiting the target Enoyl acyl carrier protein reductase were carefully chosen by making changes to the known hit molecules, here the Benzimidazole nucleus waschosen. • The designed molecules were docked against the target chosen using AutoDock 4®. • Five molecules with good docking score [lower binding energy] and interactions were shortlisted for synthesis. Reaction conditions wereoptimized. • The selected molecules were subjected to toxicity prediction assessment by OSIRIS® property explorer developed by Acetilon Pharmaceuticals limited which is available online. The results are color coded as green color which predicts the drug likeness and possibly betteractivity. • The molecules were labelled as RJ, RK, RM, RN, RO and were synthesized with satisfactoryyield. • The purity of the synthesized compounds was ensured by repeated recrystallization. Further the compounds were evaluated by TLC and Melting pointdetermination. • The characterization of the synthesized compounds was done using Infra-red, Nuclear Magnetic Resonance [H1 NMR] and Mass spectrometric methods [LC-MS]. • All the Synthesized compounds exhibited molecular ion peak (M+) of varying intensities. • The final pure compounds were screened for Anti-mycobacterial activity by in vitro method called Micro plate Alamar Blue Assay[MABA]. The synthesized compounds showed sensitivity [Minimum inhibitory concentration] at 1.6mcg/ml. The standard drugs Pyrazinamide, Ciprofloxacin and Streptomycin exhibited anti-mycobacterial activity at 3.125 mcg/ml, 3.125 mcg/ml and 6.25mcg/ml concentrations respectively. This indicates that the synthesized compounds are as Potent as the standarddrugs. • The selected compounds showed IC50 Values of 37.63, 111.2μg/ml respectively for RJ,RK