Design, Synthesis, Antimicrobial and Ergosterol Inhibition Activity of New 4-(Imidazo[1,2-a]Pyridin-2-yl)Quinoline Derivatives

Abstract

In the search for new lead compounds targeting fungi and bacteria, based on the in silico molecular docking binding affinity analysis against sterol 14-demethylase enzyme, a series of 4-(imidazo[1,2-a]pyridin-2-yl)quinoline (6a-l) have been synthesized by a cyclo condensation reaction of 4-(2-bromoacetyl)quinolin-1-ium bromide (4a-d) with substituted 2-aminopyridine (5a-c). The newly synthesized 4-(imidazo[1,2-a]pyridin-2-yl)quinoline derivatives were characterized by spectroscopic techniques. The imidazo[1,2-a]pyridinyl-quinoline derivatives were studied for ADME analysis and molecular docking against sterol 14-demethylase, enzyme essential in ergostrol biosynthesis in fungi. All compounds were evaluated for in vitro antifungal activity against Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504) and in vitro antibacterial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178). Nine 4-(imidazo[1,2-a]pyridin-2-yl)quinoline derivatives 6b, 6d, 6e, 6f, 6g, 6h, 6i, 6j and 6l, reported good antifungal activity against A. niger with MIC 62.5 µg/mL. To substantiate the mode of action compounds 6b, 6e, 6f, 6g and 6h were investigated for ergosterol inhibition assay against A. niger cells sample at 62.5 µg/mL concentration. The sterol inhibition assay analysis revealed that the ergosterol biosynthesis has decreased in the fungal samples treated with the 4-(imidazo[1,2-a]pyridin-2-yl)quinoline derivatives. Thus the substantial antifungal activity of 4-(imidazo[1,2-a]pyridin-2-yl)quinoline derivatives against A. niger suggested that these compounds could aid and assist in the development of lead compounds to treat fungal infections.