Synthesis and Pharmacological Evaluation of Hexafluoro Functionalized Quinolone Derivatives as Potential Chemotherapeutic Agents

Fluoroquinolones are broad spectrum antibiofilm agents. Herein, synthesized are a series of hexafluoro functionalized quinoline-3-carboxylate derivatives (4 a-7 d) from aryl amines as novel chemotherapeutic agents. The compound ethyl 5-chloro-6-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (4 b) exhibited the most potent promising antimicrobial and antibiofilm activity against Gram-positive Staphylococcus aureus MTCC96 with a minimum bactericidal concentration (MBC) value of 1.8 mu g/mL and an IC50 value of 15.6 +/- 0.04 mu M. The presence of ester linkage, electron withdrawing chlorine ortho (5-Cl) to hexafluoro-2-propanol and an unsubstituted nitrogen in the quinolone scaffold enhanced the antimicrobial activity. The compounds ethyl 5-chloro-6-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (4 b), ethyl 8-chloro-1-ethyl-6-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (5 d) and 6-(2-ethoxy-1,1,1,3,3,3-hexafluoropropan-2-yl)-1-ethyl-8-fluoro-4-oxo-1,4-dihydro quino- line-3-carboxylic acid (6 c) have displayed a significant cytotoxicity towards cancer cells without any toxic effects towards the normal cells.

Automated summary

This study synthesized a series of functionalized quinoline-3-carboxylate derivatives and found that one compound exhibited potent antimicrobial and antibiofilm activity against Staphylococcus aureus. Additionally, this compound displayed significant cytotoxicity towards cancer cells without any toxic effects towards normal cells.