Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid
| Autor: | Palaniappan Senthilkumar, Dharmarajan Sriram, Valakunja Nagaraja, Perumal Yogeeswari, Arnab China, Murugesan Dinakaran |
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| Rok vydání: | 2008 |
| Předmět: |
Stereochemistry
medicine.drug_class Mycobacterium smegmatis Clinical Biochemistry Antitubercular Agents Nitro compound Pharmaceutical Science Microbial Sensitivity Tests Antimycobacterial Biochemistry DNA gyrase Mycobacterium Mycobacterium tuberculosis Structure-Activity Relationship chemistry.chemical_compound Drug Resistance Multiple Bacterial Drug Discovery medicine Animals Lung Molecular Biology Antibacterial agent chemistry.chemical_classification biology Chemistry Organic Chemistry Isoniazid Quinoline biology.organism_classification Quinolines Molecular Medicine Spleen medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:3408-3418 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2007.11.016 |
| Popis: | Various 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid derivatives were synthesized from 2-aminothiophenol by a five-step reaction, evaluated for in-vitro and in-vivo antimycobacterial activities 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 supercoiling activity of DNA gyrase from M. smegmatis. Among the thirty-four synthesized compounds, 2-(3-(diethylcarbamoyl)piperidin-1-yl)-)-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid (7l) was found to be the most active compound in vitro with MIC of 0.18 and 0.08 μM against MTB and MTR-TB, respectively. Compound 7l was found to be 2 and 570 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in-vivo animal model 7l decreased the bacterial load in lung and spleen tissues with 2.78 and 3.12 − log 10 protections, respectively, at the dose of 50 mg/kg body weight. |
| Databáze: | OpenAIRE |
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