Synthesis and antibacterial properties of new 8-nitrofluoroquinolone derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2007-06, Vol.12 (6), p.1240-1258
• Main Authors: Al-Hiari, Yusuf M, Al-Mazari, Inas Saleh, Shakya, Ashok K, Darwish, Rula M, Abu-Dahab, Rana
• Format: Article
• Language: English
• Subjects: 8-Nitrofluoroquinolone Derivatives; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial Properties; Biological activity; Fluoroquinolone; Fluoroquinolones - chemical synthesis; Fluoroquinolones - chemistry; Fluoroquinolones - pharmacology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Hydrophobic and Hydrophilic Interactions; Investigations; Microbial Sensitivity Tests; Pharmacy; Spectrum Analysis; Structure-Activity Relationship
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/12061240

The objective of this research was the preparation of new 8-nitrofluoroquinolone models and investigation of their antibacterial properties. The work initially involved large scale preparation of the synthon 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3), followed by introduction of substituted primary amine appendages at the C-7 position to give derivatives 9a-g, in which the amino group is appended to substituted benzenes or aromatic heterocycles, is part of a primary alpha-amino acid or just a simple primary aliphatic amine. This nucleophilic aromatic substitution step was a very simple procedure since the 8-nitro group of the above synthon facilitated the addition of weak nucleophiles at C-7. All compounds prepared were fully identified and characterized using NMR, IR, EA and MS, and were consistent with expected structures. The prepared targets and the intermediates have shown interesting antibacterial activity against gram positive and/or gram negative strains. In particular, the p-toluidine, p-chloroaniline and aniline derivatives showed good activity against S. aureus with MIC range approximately 2-5 microg/mL. In conclusion, more lipophilic groups seem to enhance activity against gram positive strains.