Synthesis, antimicrobial evaluation, and computational studies of a novel series of 4,7-disubstituted quinoline derivatives incorporating acetamide-substituted piperazine and thiosemicarbazide motifs

The growing threat of antimicrobial resistance necessitates the development of new antibiotics with diverse mechanisms of action. In this study, a series of novel N-(substituted)phenyl-2-(4-(7-(2-((substituted)phenylcarbamothioyl)hydrazinyl)quinolin-4-yl)piperazin-1-yl)acetamide derivatives (6a–m) was synthesized using multistep reactions. A modified Ullmann coupling strategy was employed to introduce hydrazine hydrate at the 7th position of 4,7-dichloroquinoline involving copper metal in varying oxidation states. This work adopts a hybridization strategy by integrating quinoline, piperazine, thiosemicarbazide, and quinoline pharmacophores to explore synergistic antimicrobial effects. The final compounds were characterized by ¹H NMR, ¹³C NMR, and mass spectrometry. Molecular docking studies against E. coli DNA gyrase B (GyrB; PDB ID: 5L3J) revealed favorable binding affinities, ranging from − 5.97 to − 7.96 kcal/mol. These findings suggest scope for further biological evaluation using the agar dilution method, which demonstrated moderate antibacterial and antifungal activity compared to standard drugs. While the compounds did not surpass the reference drugs, the combination of docking results and moderate in vitro activity indicates that these scaffolds may serve as a basis for future chemical modification and development against resistant microbial strains.