Synthesis and Antimycobacterial Evaluation on Arylsulfonyl and Arylcarbonyl Derivatives of Ofloxacin |
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Authors: | Yeh‐Long Chen Yu‐Wen Chen We‐Fen Lo Chai‐Lin Kao Yu‐Shuan Liu Chen‐Wen Yao Chemg‐Chyi Tzeng |
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Institution: | 1. Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan, R.O.C.;2. Department of Pathology, Tri‐Service General Hospital, Taipei 114, Taiwan, R.O.C. |
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Abstract: | Four ofloxacin derivatives 3, 5, 6 , and 11 were found to exhibit > 90% inhibition on the growth of M. tuberculosis at a concentration of 6.25 μg/mL. Compounds 3, 5 and 11 have also exhibited a broad spectrum of antibacterial activities while 8‐fluoro‐3‐methyl‐9‐4‐(4‐nitrophenylsulfonyl)piperazin‐1‐yl)‐6‐oxo‐2,3‐dihydro‐6H‐1‐oxo‐3a‐azaphenalene‐5‐carboxylic acid ( 6 ), which exhibited potent activity against the growth of TB with the MIC of 2.23 μg/mL and a selectivity index (SI) of > 14.80, was inactive against the growth of G(+)‐ and G(‐)‐bacteria. Selective anti‐TB activity was achieved by the introduction of an arylsulfonyl group at C‐7 piperazin‐4‐yl of N‐demethyl ofloxacin. Compound 6 is species‐specific, exhibiting no significant activity against the growth of bacterial species other than M. tuberculosis, which implied the possibility of developing new specific anti‐TB drug candidates without inducing cross resistance with other currently used antibacterial drugs. Structural optimization of 6 is on‐going. |
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Keywords: | Fluoroquinolone Antimycobacterial activity Ofloxacin derivatives |
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