Synthesis, antimycobacterial and antibacterial activity of ciprofloxacin derivatives containing a N-substituted benzyl moiety

We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was evaluated. Results reveal that compound 4f has good in vitro activity against all of the tested Gram-positive strains including MRSA and MRSE (MICs: 0.06-32 mu g/mL) which is two to eightfold more potent than or comparable to the parent drug CPFX (MICs: 0.25-128 mu g/mL), Gram-negative bacteria P. aeruginosa (MICs: 0.5-4 mu g/mL) and M. tuberculosis H37Rv ATCC 27294 (MIC: 1 mu g/mL). (C) 2012 Elsevier Ltd. All rights reserved.