Design Synthesis and Antimicrobial Evaluation of Fluoroquinolone Thiadiazole Hybride: Agents Against Antimicrobial Infection

ABSTRACT Background: The increasing prevalence of antimicrobial resistance has heightened the need for novel therapeutic agents to treat infections effectively. Among various classes of antibiotics, fluoroquinolones have been widely used due to their broad-spectrum activity and ability to inhibit bacterial DNA gyrase and topoisomerase IV enzymes, which are essential for bacterial DNA replication. However, the efficacy of fluoroquinolones has been significantly compromised by emerging bacterial resistance. The design strategy involved molecular docking studies to optimize binding interactions of the fluoroquinolone-thiadiazole hybrids with bacterial enzymes, aiming to improve potency and spectrum of activity. Result: The synthesis pathway was streamlined to ensure feasibility in a laboratory setting, with intermediates purified and characterized using advanced analytical techniques like NMR, MS, and IR spectroscopy. The synthesized compounds were subjected to in vitro antimicrobial evaluation against a panel of Gram-positive and Gram-negative bacteria, including drug-resistant strains. Minimum inhibitory concentration (MIC) values were determined to assess potency, and the fluoroquinolone-thiadiazole hybrids displayed significant antimicrobial activity compared to traditional fluoroquinolones. Furthermore, structure-activity relationship (SAR) analysis highlighted the importance of substitutions on the thiadiazole ring, revealing that electron-donating groups at specific positions contributed to increased antimicrobial activity. Conclusion: The findings suggest that the fluoroquinolone-thiadiazole hybrid scaffold holds promise as an effective antimicrobial agent against multidrug-resistant infections, providing a novel direction for the development of future antibacterial agents. Keywords: Fluoroquinolone thiadiazole hybrid, antimicrobial resistance, bacterial DNA gyrase inhibition, structure-activity relationship (SAR), broad-spectrum antibiotics, antimicrobial evaluation