2. Academic Validation
  3. 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

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

  • Bioorg Med Chem. 2008 Mar 1;16(5):2558-69. doi: 10.1016/j.bmc.2007.11.050.
Palaniappan Senthilkumar 1,  Murugesan Dinakaran,  Debjani Banerjee,  Ruth Vandana Devakaram,  Perumal Yogeeswari,  Arnab China,  Valakunja Nagaraja,  Dharmarajan Sriram
Affiliations

Affiliation

  • 1 Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
PMID: 18078756 DOI: 10.1016/j.bmc.2007.11.050
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)-yl)-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 microM 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 50mg/kg body weight. Compound 13n also inhibited the supercoiling activity of mycobacterial DNA gyrase with IC(50) of 30.0 microg/ml.

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