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

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• 作者：Dharmarajan Sriram ; Palaniappan Senthilkumar ; Murugesan Dinakaran ; Perumal Yogeeswari ; Arnab China ; Valakunja Nagaraja
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 29, 2007
• 年：2007
• 卷：50
• 期：24
• 页码：6232 - 6239
• 全文大小：197K
• 年卷期：v.50,no.24(November 29, 2007)
• ISSN：1520-4804

文摘

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 invivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug-resistant Mycobacterium tuberculosis(MDR-TB) and Mycobacterium smegmatis (MC²) and also tested for the ability to inhibit the supercoilingactivity 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 bethe most active compound in vitro with an MIC of 0.1 M against MTB and MDR-TB and was 3 and 455times more potent than isoniazid against MTB and MDR-TB, respectively. In the in vivo animal model 10qdecreased the bacterial load in lung and spleen tissues with 2.39 and 3.89-log10protections respectively atthe dose of 50 mg/kg body weight.