Synthesis, and Computational Insights Into Quinoline Hydrazide Derivatives as Potential Antimicrobial Agents

A series of novel quinoline hydrazide derivatives (4a-4o) were synthesized and characterized by mass spectrometry, ¹H NMR, and ¹³C NMR. The compounds exhibited notable antibacterial and antifungal activity. Among gram-positive strains, compounds 4f and 4j showed potent inhibition against Bacillus subtilis (MIC = 0.033 and 0.015 mM), while compound 4o was highly active against Streptococcus pneumoniae (MIC = 0.139 mM). Against gram-negative bacteria, compounds 4d and 4n were most effective against E. coli (MIC = 0.150 and 0.112 mM). Molecular docking and 100 ns molecular dynamics simulations revealed stable binding of compounds 4d and 4n with E. coli DNA gyrase B, primarily through hydrogen bonding and π-cation interactions. DFT studies supported their electronic reactivity, and in silico ADMET profiling predicted high intestinal absorption and favorable pharmacokinetic properties. Overall, the results highlight quinoline hydrazide derivatives as promising candidates for antimicrobial drug development.