Synthesis of Imidazo[1,2-b]pyridazine Scaffold Based Amide Derivatives as Potential Inhibitors for Bacterial Activity

A series of fifteen novel amide derivatives based on imidazo[1,2-b]pyridazine scaffold were synthesized by taking imidazo[1,2-b]pyridazine-3-carboxylic acid intermediates with respective substituted amines to yield good to excellent. The molecular structures of the newly synthesized compounds were elucidated using spectroscopic techniques (H-1 NMR, C-13 NMR, and LCMS) and supported by single-crystal X-ray diffraction (SXRD) for the two compounds, 9 and 18. These compounds were evaluated in vitro for antimicrobial activity against two Gram-positive bacteria (S. aureus and B. subtilis) and two Gram-negative bacteria (E. coli and P. aeruginosa). Interestingly, compounds 10 and 16, displayed comparable antibacterial activity to the positive control (Tetracycline: 6.25 mu g/mL) against Gram-negative bacteria, particularly Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 6.25 mu g/mL. Compound 17 exhibited moderate antibacterial activity with an MIC of 10 mu g/mL against the Gram-positive bacterium Bacillus subtilis, whereas the positive control demonstrated an MIC of 6.25 mu g/mL. These antibacterial activities were found to have a good correlation with Insilco computational molecular docking experiments using the receptor UDP-N-acetylglucosamine-enolpyruvate reductase, Mtb MurB.