Synthesis, in vitro evaluation of antimicrobial and molecular docking study of quinoline-based imine and amide derivatives

The quinoline scaffold is a nitrogen-containing heterocyclic compound widely used in chemical and pharmaceutical research. The purpose of this article is to synthesize new quinoline imines and amide and evaluate their antimicrobial activities using in vitro and in silico methods. Most of the purification process involves silica gel chromatography which lowers the yield after each process as a prime challenge of this synthesis which further limits possible structural diversification. The Vilsmeier-Haack reaction, aromatic nucleophilic substitution and condensation reactions were used to synthesize five quinoline imines and one amide. The synthesized compounds were characterized using NMR and FTIR spectroscopy. The antimicrobial activities of these compounds were evaluated using disc diffusion and microdilution methods against four bacteria strains (E. coli, S. aureus, K. pneumoniae and S. pyogenes) and three fungal strains (Candida albicans, Aspergillus flavus, and Aspergillus niger). All of the synthesized compounds showed moderate antibacterial properties and very good antifungal activities. Specifically, one of synthetic derivatives (compound 11), exhibited stronger antifungal activity than the reference drug used. The binding interactions patterns and the binding affinities of these compounds were investigated against E. coli DNA gyrase and Candida albicans sterol 14α-demethylase by molecular docking analysis. The docking analysis results were in good agreement with the in vitro evaluation data. Thus, both invitro and in silico results showed better antifungal activity.