Synthesis, characterization, in silico and in vitro antimicrobial evaluation of some quinoline derivatives

Abstract

A series of quinoline derivatives (4a–k) have been synthesized and tested to assess ADMET properties, docking behaviour, and antibacterial potential. A series of various quinoline derivatives have been synthesized by a simple and efficient three-component reaction using anilines, aromatic aldehydes and ethyl acetoacetate with acetonitrile as a solvent. The characterization of the synthesized compounds have been done by IR and NMR spectroscopy. Compound 4d shows the highest binding affinity of −8.4 kcal/mol. Strong interactions that involved key amino acids have also been observed. ADMET analysis reveals outstanding intestinal absorption and CNS permeability. The antibacterial activity of synthesized quinoline derivatives have been evaluated using the agar diffusion method against two Gram-positive and two Gram-negative bacteria, with ciprofloxacin as the standard. Compounds 4c, 4d, and 4j show broad-spectrum activity, with 4c demonstrating the most consistent and potent inhibition, surpassing ciprofloxacin against B. subtilis and E. coli, making it a promising lead for further development. Two-way ANOVA analysis shows no statistically significant difference in antibacterial activity among the tested compounds (p = 0.891) or bacterial strains (p = 0.431), indicating a uniform response. However, Tukey’s HSD test confirmed that no compound could significantly outperform ciprofloxacin