Sriram, Dharmarajan and Senthilkumar, Palaniappan and Dinakaran, Murugesan and Yogeeswari, Perumal and China, Arnab and Nagaraja, Valakunja (2007) Antimycobacterial Activities of Novel 1-(Cyclopropyl/tert-butyl/4-fluorophenyl)-1,4-dihydro-6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic Acid. In: Journal of Medicinal Chemistry, 50 (24). pp. 6232-6239.
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Fifty-one 1-(cyclopropyl/tert-butyl/4-fluorophenyl)-1,4-dihydro-6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic acids were synthesized and evaluated for antimycobacterial in Vitro and in ViVo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis $(MC^2)$ and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 1-tert-butyl-1,4-dihydro-7-(4,4-dimethyloxazolidin-3-yl)-6-nitro-4-oxo-1,8-naphthyridine-3-carboxylic acid (10q) was found to be the most active compound in Vitro with an MIC of $0.1 \mu M$ against MTB and MDR-TB and was 3 and 455 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in ViVo animal model 10q decreased the bacterial load in lung and spleen tissues with 2.39 and 3.89-log10protections respectively at the dose of 50 mg/kg body weight.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to American Chemical Society.|
|Department/Centre:||Division of Biological Sciences > Microbiology & Cell Biology|
|Date Deposited:||16 Sep 2008 09:59|
|Last Modified:||19 Sep 2010 04:49|
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