Synthesis, Antimycobacterial Activities and Phototoxic Evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic Acid Derivatives

Author(s): Murugesan Dinakaran, Palaniappan Senthilkumar, Perumal Yogeeswari, Arnab China, Valakunja Nagaraja, Dharmarajan Sriram

Journal Name: Medicinal Chemistry

Volume 4 , Issue 5 , 2008

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Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi 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 synthesized compounds, 8-[6-[[(1,1- dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4- carboxylic acid (10q) was found to be the most active compound in vitro with MIC of 0.08 μM and < 0.08 μM against MTB and MDR-TB respectively. Compound 10q was found to be 4.5 and > 570 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 2.51 and 3.71-log10 protections respectively at the dose of 50 mg/kg body weight.

Keywords: Antimycobacterial activity, antitubercular activity, tuberculosis, thiazoloquinolone

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Article Details

Year: 2008
Page: [482 - 491]
Pages: 10
DOI: 10.2174/157340608785700225
Price: $65

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