Antituberculosis agents. IX. In vitro antimycobacterial activity of N-(2-phenyl-2-oxoethyl) and N-[2-(4-fluorophenyl)-2-oxoethyl]ciprofloxacin derivatives against some drug-resistant strains of Mycobacterium tuberculosis and Mycobacterium avium isolates.

Abstract

The in vitro antimycobacterial activity of two ciprofloxacin analogues (2a and 2b) containing 2-phenyl-2-axoethyl and 2-(4-fluorophenyl)-2-axoethyl groups attached to N-4 position of piperazin ring, was evaluated against M. tuberculosis strains resistant to Isoniazid (MIC 2a and 2b = 3.13 micrograms/ml), Ethambutol (MIC 2a and 2b = 1.56 micrograms/ml), Rifampin (MIC 2a and 2b = 1.56 micrograms/ml), Kanamycin (MIC 2a and 2b = 1.56 micrograms/ml) and ciprofloxacin (MIC 2a and 2b > 25 micrograms/ml). Furthermore, the minimum bactericidal concentration (MBC) of 2a and 2b was determined against M. tuberculosis H37Rv (MBC2a = 6.25 and 2b = 25 micrograms/ml) and strains resistant to isoniazid (MBCs > 25 micrograms/ml) and rifampin (MBC2a = 3.13 and 2b = 6.25 micrograms/ml). Also, in this study the activity of 2a and 2b was determined against a strain of M. avium (%Inhibition 2a = 89 and 2b = 95%). Expanded primary screening was conducted for 2b (having MIC < 6.25 micrograms/ml) against five clinical isolates of M. avium using the MABA and BACTEC 460 systems (MIC = 2-4 micrograms/ml). The significant anti-Mycobacterium avium activity of 2b suggested further M. avium assays and so, 2b was then retested at lower concentrations against 30 strains of M. avium including five strains resistant to claritromycin (MIC = 2-16 micrograms/ml).