| Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological evaluation. | |
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MedLine Citation:
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PMID: 18068979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities 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 mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 microM and 0.09 microM against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91--log10 protections, respectively, at the dose of 50mg/kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC(50) of 10.0 microg/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections. |
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Authors:
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Murugesan Dinakaran; Palaniappan Senthilkumar; Perumal Yogeeswari; Arnab China; Valakunja Nagaraja; Dharmarajan Sriram |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-04 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 18 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-05 Completed Date: 2008-03-24 Revised Date: 2013-04-24 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 1229-36 Citation Subset: IM |
Affiliation:
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Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antitubercular Agents / chemical synthesis*, chemistry, pharmacology* Combinatorial Chemistry Techniques DNA Gyrase / antagonists & inhibitors*, metabolism Enzyme Inhibitors / chemical synthesis, chemistry, pharmacology Fluoroquinolones / chemical synthesis, chemistry*, pharmacology* Lung / drug effects, microbiology Mice Molecular Structure Mycobacterium tuberculosis / drug effects*, enzymology* Ofloxacin / pharmacology Spleen / drug effects, microbiology Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Antitubercular Agents; 0/Enzyme Inhibitors; 0/Fluoroquinolones; 82419-36-1/Ofloxacin; EC 5.99.1.-/DNA Gyrase; L4618BD7KJ/gatifloxacin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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