Synthesis and evaluation of novel 1,3,4-thiadiazole–fluoroquinolone hybrids as antibacterial, antituberculosis, and anticancer agents

Abstract

A series of 5-substituted-1,3,4-thiadiazole-based fluoroquinolone derivatives were designed as potential antibacterial and anticancer agents using a molecular hybridization approach. The target compounds 16–25 were synthesized by reacting the corresponding N -(5-substituted-1,3,4-thiadiazol-2-yl)-2-chloroacetamides with ciprofloxacin ornorfloxacin. The purity and identity of the synthesized compounds were determined by the use of chromatographicand spectral techniques (NMR, IR, MS, etc.) besides elemental analysis. Antibacterial, antituberculosis, and anticancer activity of the target compounds were evaluated against selected strains and cancer cell lines. Compound 20was appreciated as the most active agent representing antibacterial activity against Escherichia coli and Staphylococcusaureus with MIC values of 4 µg/mL and 2 µg/mL, respectively. Amongst the synthesized fluoroquinolone derivatives,compounds 19 and 20 were found to have modest antitubercular activity with 8 µg/mL MIC values for each. Mostpotent derivative, compound 20 was docked against Staphylococcus aureus and Mycobacterium tuberculosis DNA gyraseenzymes to visualize the possible conformation of the compound. Additionally, anticancer activities of target compoundswere evaluated on seven different cancer cell lines.