Synthesis of Phenoxy Substituted Imidazo[1,2-b]Pyridazine-Based Amide Derivatives for Antibacterial and Anti-Tubercular Activities.

Abstract

A series of 10 phenoxy-substituted imidazo[1,2-b]pyridazine amide derivatives were synthesized from 6-chloro-2-methyl-8-phenoxyimidazo[1,2-b]pyridazine-3-carboxylic acid and respective amines. All these 10 compounds were characterized using spectroscopic analysis (¹H, ¹³C, HPLC, and ESI). Furthermore, the molecular structure obtained with spectroscopic analysis was confirmed by single-crystal x-ray diffraction (SXRD) analysis with a compound 12. All the 10 newly synthesized compounds were screened for in vitro antibacterial activities with the agar dilution method against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Compounds 11 and 13 both showed MIC values, 6.25 µg/mL, and comparable antibacterial activity to the positive control with the reference drug. Similarly, Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA) and compounds 9 and 12 displayed moderate tubercular activities at a concentration of 25 µg/mL. The molecular docking studies correlated with biological activity against the active sites of PDB ID: 5JZX.