Synthesis and antimycobacterial activities of novel 6-nitroquinolone-3-carboxylic acids

Eur J Med Chem. 2009 Jan;44(1):345-58. doi: 10.1016/j.ejmech.2008.02.031.

Palaniappan Senthilkumar ¹, Murugesan Dinakaran, Perumal Yogeeswari, Dharmarajan Sriram, Arnab China, Valakunja Nagaraja

Affiliations

Affiliation

1 Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.

PMID: 18502542 DOI: 10.1016/j.ejmech.2008.02.031

Abstract

Various 1-(substituted)-1,4-dihydro-6-nitro-4-oxo-7-(sub-secondary amino)-quinoline-3-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid by six step synthesis. The compounds were evaluated for antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC(2)) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the 48 synthesized compounds, 7-(4-((benzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-1-cyclopropyl-1,4-dihydro-6-nitro-4-oxoquinoline-3-carboxylic acid (8c) was found to be the most active compound in vitro with MIC of 0.08 and 0.16 microM against MTB and MDR-TB, respectively. In the in vivo animal model 8c decreased the Bacterial load in lung and spleen tissues with 2.78 and 4.15-log10 protections, respectively, at the dose of 50 mg/kg body weight.

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