Design, synthesis, single-crystal X-ray and docking studies of imidazopyridine analogues as potent anti-TB agents

With the intent to discover new anti-TB compounds, new imidazopyridine analogues were synthesized through Schiff-base reaction. The newly developed imidazopyridines (I1-I8) were characterized using spectroscopic and elemental analysis. In addition the structure of compound I3 was elucidated by the single crystal X-ray diffraction technique. The global chemical reactivity descriptor parameter was calculated using theoretically DFT-B3LYP-6-31G(d) basis set which estimated HOMO-LUMO value and results are discussed. All the newly synthesized compounds were screened for their in vitro anti-tubercular activity, while the most active compounds were subjected to a cytotoxicity assay on Vero cell lines. Most of the tested compounds exhibited significant anti-TB activity with MIC in the range 3.12 - 12.5 mu g/mL. Among the synthesized, compound I2 and I7 were found to be more active than the standard anti-TB drug streptomycin and comparable activity to pyrazinamide. A cytotoxicity study on Vero-cell lines confirmed the nontoxic nature of compound I2 and I7 indicating good safety profile. The molecular docking studies on PDB IB: 4ED4 enzyme of Mycobacterium tuberculosis was conducted to investigate mechanisms of anti-TB activity. The compounds displayed excellent hydrogen binding interactions and docking scores against MTB, which were in accordance with the results and further supported its credibility.