Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids

Senthilkumar, Palaniappan and Dinakaran, Murugesan and Banerjee, Debjani and Devakaram, Ruth Vandana and Yogeeswari, Perumal and China, Arnab and Nagaraja, Valakunja and Sriram, Dharmarajan (2008) Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids. In: Bioorganic & Medicinal Chemistry, 16 (5). pp. 2558-2569.

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Abstract

Thirty-four newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids were synthesized from 1,2,3,4-tetrafluoro benzene and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis $(MC^2)$ and also tested for the ability to inhibit the supercoiling activity of DNA gyrase. Among the synthesized compounds, 7-(1-(4-methoxybenzyl)-3,4,5,6,7,8-hexahydroisoquinolin-2(1H)- l)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxoquinoline-3-carboxylic acid (13n) was found to be the most active compound in vitro with MIC of 0.16 and 0.33 \mu M against MTB and MDR-TB, respectively. In the in vivo animal model 13n decreased the bacterial load in lung and spleen tissues with 2.54 and 2.92 - log10 protections, respectively, at the dose of 50 mg/kg body weight. Compound 13n also inhibited the supercoiling activity of mycobacterial DNA gyrase with $IC_{50}$ of 30.0 \mu g/ml.

Item Type:	Journal Article
Publication:	Bioorganic & Medicinal Chemistry
Publisher:	Elsevier
Additional Information:	Copyright of this article belongs to Elsevier.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	09 May 2008
Last Modified:	19 Sep 2010 04:44
URI:	http://eprints.iisc.ac.in/id/eprint/13923

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