title: 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.
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.
authors: Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
authors: Palaniappan
authors: P
authors: Senthilkumar
authors: Murugesan
authors: M
authors: Dinakaran
authors: Debjani
authors: D
authors: Banerjee
authors: Ruth Vandana
authors: RV
authors: Devakaram
authors: Perumal
authors: P
authors: Yogeeswari
authors: Arnab
authors: A
authors: China
authors: Valakunja
authors: V
authors: Nagaraja
authors: Dharmarajan
authors: D
authors: Sriram
mesh_terms: D000586:Amination; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003521:Cyclopropanes / Q000737:chemistry*; D027081:DNA Gyrase / Q000378:metabolism; D017611:Fluorine Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D003521:Cyclopropanes; D017611:Fluorine Compounds; D006912:Hydroxyquinolines; D017319:Photosensitizing Agents; D059005:Topoisomerase II Inhibitors; C030797:cyclopropane; D027081:DNA Gyrase