Antitubercular activities of novel benzothiazolo naphthyridone carboxylic acid derivatives endowed with high activity toward multi-drug resistant tuberculosis
| Autor: | Palaniappan Senthilkumar, Dharmarajan Sriram, Perumal Yogeeswari, Murugesan Dinakaran |
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| Rok vydání: | 2009 |
| Předmět: |
Tuberculosis
Carboxylic acid Antitubercular Agents Carboxylic Acids Microbial Sensitivity Tests Pharmacology Microbiology Mycobacterium tuberculosis Mice In vivo Chlorocebus aethiops Tuberculosis Multidrug-Resistant medicine Animals Vero Cells chemistry.chemical_classification Molecular Structure biology Chemistry Multi-drug-resistant tuberculosis Isoniazid General Medicine biology.organism_classification medicine.disease Gatifloxacin In vitro Female medicine.drug |
| Zdroj: | Biomedicine & Pharmacotherapy. 63:11-18 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2007.10.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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