Antitubercular activities of novel benzothiazolo naphthyridone carboxylic acid derivatives endowed with high activity toward multi-drug resistant tuberculosis.

Murugesan Dinakaran, Palaniappan Senthilkumar, Perumal Yogeeswari, Dharmarajan Sriram

文献索引：Biomed. Pharmacother. 63 , 11-18, (2009)

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摘要

Sixteen novel 3-nitro-2-(sub)-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acids were synthesized from 2,6-dimethoxynicotinic acid and 2-aminothiophenol and evaluated for their antitubercular activities in vitro and in vivo against Mycobacterium tuberculosis H(37) Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among the synthesized compounds, 2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acid (10n) was found to be the most active compound in vitro with MIC of 0.19 and 0.04 microM against MTB and MTR-TB, respectively. Compound 10n showed promising activity against MDR-TB and was 208 and 1137 times more potent than gatifloxacin and isoniazid, respectively. In the in vivo animal model 10n decreased the mycobacterial load in lung and spleen tissues with 2.81 and 4.94-log(10) protections, respectively, at a dose of 50 mg/kg body weight.