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

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

Volume: 4 Issue: 5

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

Affiliation:

Keywords: Antimycobacterial activity, antitubercular activity, tuberculosis, thiazoloquinolone

Abstract: 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.

Cite this article as:

Dinakaran Murugesan, Senthilkumar Palaniappan, Yogeeswari Perumal, China Arnab, Nagaraja Valakunja and Sriram Dharmarajan, Synthesis, Antimycobacterial Activities and Phototoxic Evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic Acid Derivatives, Medicinal Chemistry 2008; 4 (5) . https://dx.doi.org/10.2174/157340608785700225