title: Antimycobacterial activities of novel fluoroquinolones.
abstract: Fifty-one novel 1-(cyclopropyl/2,4-difluorophenyl/t-butyl)-1,4-dihydro-6-fluoro-7-(sub secondary amino)-4-oxoquinoline-3-carboxylic acids were synthesized and evaluated for their 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 synthesized compounds, 7-(3-(diethylcarbamoyl)piperidin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (7l) was found to be the most active compound in vitro with MIC of 0.09 microM against MTB and MDR-TB respectively. In the in vivo animal model 7l decreased the mycobacterial load in lung and spleen tissues with 2.53- and 4.88-log10 protections respectively at a dose of 50mg/kg body weight.
authors.affiliation: Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani, Rajasthan, 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: Arnab
authors.initials: A
authors.lastname: China
authors.forename: Valakunja
authors.initials: V
authors.lastname: Nagaraja
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D017484:Dermatitis, Phototoxic; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000201:enzymology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase