Design, synthesis, and structure–activity relationship of 2-chloro-3-formylquinoline containing hybrids as powerful antibacterial agents

Abstract

This work aims to evaluate the antimicrobial activity of some new quinoline derivatives linked to pyrazole derivatives. The target compounds pyrazolylvinylquinoline 11a-g and 12a-g were achieved by the reaction of 2-chloro-6-nitro-3-quinolinecarboxaldehyde (4) with bromotriphenylphosphonylmethylpyrazole derivatives 9a,b to give the new quinoline derivatives 10a,b which in turn reacted with different aryl amines to afford 11a-g and 12a-g. Pyrazole derivatives 9a,b were obtained by the reaction of hydroxymethylpyrazole derivatives 8a,b with triphenylphosphine hydrobromide. Antimicrobial evaluation of the newly synthesized compounds showed that most of the new compounds appeared active toward Gram-positive bacteria more than Gram-negative bacteria. The biological evaluation of compounds 12d-g displayed the highest antimicrobial activity against the tested microorganism strains. Additionally, compounds 12d and 12f showed excellent activity against P. aeruginosa (MIC50 0.019 mg/mL), while compounds 11d, 11f, 12e, and 12g displayed good activity against the same microorganism (MIC50 0.07 mg/mL). On the other hand, most of the new compounds have moderate activity against E. coli. Compounds 12d and 12f showed excellent activity versus C. albicans in vitro antifungal activity (MIC50 0.15 mg/mL) comparing to or slightly lower than that of Fluconazole. Using molecular docking simulations, we evaluated the binding affinities and interactions of four chosen derivatives 12d-g with a target PDB code 3WT0 protein.