title: Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid.
abstract: Various 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid derivatives were synthesized from 2-aminothiophenol by a five-step reaction, evaluated for in-vitro and in-vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the thirty-four synthesized compounds, 2-(3-(diethylcarbamoyl)piperidin-1-yl)-)-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid (7l) was found to be the most active compound in vitro with MIC of 0.18 and 0.08 microM against MTB and MTR-TB, respectively. Compound 7l was found to be 2 and 570 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in-vivo animal model 7l decreased the bacterial load in lung and spleen tissues with 2.78 and 3.12-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: Murugesan
authors.initials: M
authors.lastname: Dinakaran
authors.forename: Palaniappan
authors.initials: P
authors.lastname: Senthilkumar
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 / Q000737:chemistry* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D008168:Lung / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000382:microbiology; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D011804:Quinolines