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

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Antimicrobial Drug Discovery

Background:

• Growing antimicrobial resistance necessitates the development of new therapeutic agents.
• Quinoline scaffolds are recognized for their diverse biological activities, including antimicrobial properties.

Purpose of the Study:

• To synthesize and characterize novel quinoline hydrazide derivatives.
• To evaluate the in vitro antibacterial and antifungal potential of these derivatives.
• To investigate the molecular interactions and pharmacokinetic properties of lead compounds.

Main Methods:

• Synthesis and structural elucidation of quinoline hydrazide derivatives (4a-4o) using spectroscopic techniques (Mass Spectrometry, ¹H NMR, ¹³C NMR).
• Determination of minimum inhibitory concentrations (MICs) against various Gram-positive and Gram-negative bacterial strains, and fungal strains.
• Computational studies including molecular docking, molecular dynamics simulations, DFT analysis, and in silico ADMET profiling.

Main Results:

• Compounds 4f, 4j, and 4o exhibited potent activity against Gram-positive bacteria (Bacillus subtilis, Streptococcus pneumoniae).
• Compounds 4d and 4n displayed significant efficacy against Gram-negative bacteria, specifically E. coli.
• Molecular simulations confirmed stable binding of 4d and 4n to E. coli DNA gyrase B, with favorable predicted pharmacokinetic profiles.

Conclusions:

• The synthesized quinoline hydrazide derivatives possess significant antimicrobial potential.
• Compounds 4d and 4n are identified as lead candidates for further development as antibacterial agents targeting E. coli.
• The study supports the exploration of quinoline hydrazides as a promising class for novel antimicrobial drug development.