Exploring the Anti-tubercular Potential of 2-(1H-Pyrazol-1-yl) Pyrimidine: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.

We designed and synthesized pyrazolyl pyrimidine containing derivatives and screened for anti-mycobacterial activity. Different spectral techniques like HRMS, 1H, and 13C NMR are deployed for the structural confirmation of the final derivatives. Final compounds were screened against the Mycobacterium tuberculosis (Mtb) H37Rv strain. Using MABA (Microplate Alamar Blue Assay), the concentration of the compound required to inhibit bacterial growth was assessed. Rifampicin was used as a standard in the biological evaluation of the synthesized compounds whose minimum inhibitory concentration (MIC) is 3.12 µg/mL. MIC values of the synthesized compounds varied from 6.25 µg/mL to 25 µg/mL. Three derivatives, F-2, F-5 and F-9among the synthesized, are most active with MIC values of 6.25 µg/mL. F-2, F-5 and F-9 compounds were also screened for their cytotoxicity against normal cells, where F-9 has shown selectivity over normal human embryonic kidney cell line (HEK293T). Insilico ADME was evaluated using the SWISS ADME tool. Docking studies were carried out for the compounds, F-2, F-5 and F-9 at the active site of the crystal structure InhA (PDB ID: 4TZK), the enoyl acyl carrier protein reductase. MD simulations were carried for the strongly docked F-9 compound to assess the stability of protein ligand complex.