Synthesis, and Antimycobacterial and Cytotoxic Evaluation of Certain Fluoroquinolone Derivatives

✍ Scribed by Jia-Yuh Sheu; Yeh-Long Chen; Cherng-Chyi Tzeng; Shu-Lin Hsu; Kuo-Chang Fang; Tai-Chi Wang

• Book ID: 102255198
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: German
• Weight: 126 KB
• Volume: 86
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200390201

✦ Synopsis

Abstract

Certain 1‐ethyl‐ and 1‐aryl‐6‐fluoro‐1,4‐dihydroquinol‐4‐one derivatives were synthesized and evaluated for antimycobacterial and cytotoxic activities. Preliminary results indicated that, for 1‐aryl‐6‐fluoroquinolones, both 7‐(piperazin‐1‐yl)‐ and 7‐(4‐methylpiperazin‐1‐yl) derivatives, 9b and 11a, are able to completely inhibit the growth of M. tuberculosis at a concentration of 6.25 μg/ml, while the 7‐[4‐(2‐oxo‐2‐phenylethyl)piperazin‐1‐yl] derivative 13 exhibits only 31% growth inhibition at the same concentration. For 1‐ethyl‐6‐fluoroquinolones, both 7‐[4‐(2‐oxopropyl)piperazin‐1‐yl]‐ and 7‐[4‐(2‐oxo‐2‐phenylethyl)piperazin‐1‐yl]‐derivatives, 2a and 2b, respectively, show complete inhibition, while their 2‐iminoethyl and substituted phenyl counterparts 3a and 2c are less active. In addition, the 6,8‐difluoro derivative was a more‐favorable inhibitor than its 6‐fluoro counterpart (2b vs. 2d). These results deserve full attention especially because 2a, 2b, 9b, and 11a are non‐cytotoxic at a concentration of 100 μM. Furthermore, compound 9b proved to be a potent anti‐TB agent with selective index (SI)>40 and an EC~90~ value of 5.75 μg/ml.