title: Synthesis and antimycobacterial activities of novel 6-nitroquinolone-3-carboxylic acids.
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.
authors.affiliation: Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
authors.forename: Palaniappan
authors.initials: P
authors.lastname: Senthilkumar
authors.forename: Murugesan
authors.initials: M
authors.lastname: Dinakaran
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.forename: Arnab
authors.initials: A
authors.lastname: China
authors.forename: Valakunja
authors.initials: V
authors.lastname: Nagaraja
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids; D002522:Chlorocebus aethiops; D027081:DNA Gyrase / Q000187:drug effects; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013158:Splenic Diseases / Q000188:drug therapy / Q000382:microbiology; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D011804:Quinolines; D027081:DNA Gyrase