title: Antimycobacterial and phototoxic evaluation of novel 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid.
abstract: Several newer 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids (10-11a-q) were synthesised from 3,4-difluoro aniline and 3-fluoro-4-nitro aniline by nine-step synthesis. The compounds were evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multidrug-resistant M. tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) as well as being tested for their ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesised compounds, 7-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-6-nitro-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (11l) was found to be the most active compound in vitro, with minimum inhibitory concentrations (MICs) of 0.09 microM and <0.09 microM against MTB and MTR-TB, respectively. Compound 11l was found to be 4 times and >506 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in vivo animal model, 11l decreased the bacterial load in lung and spleen tissues by 30% and 42%, respectively, at a dose of 50 mg/kg body weight.
authors: Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science (BITS), Pilani 333031, India.
authors: Dinakaran
authors: D
authors: Murugesan
authors: Senthilkumar
authors: S
authors: Palaniappan
authors: Yogeeswari
authors: Y
authors: Perumal
authors: China
authors: C
authors: Arnab
authors: Nagaraja
authors: N
authors: Valakunja
authors: Dharmarajan
authors: D
authors: Sriram
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D001385:Azetines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002522:Chlorocebus aethiops; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000382:microbiology; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000382:microbiology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D001385:Azetines; D004791:Enzyme Inhibitors; D011804:Quinolines; D059005:Topoisomerase II Inhibitors