| Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents. | |
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MedLine Citation:
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PMID: 15456272 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In an effort to develop new and more potent therapies to treat tuberculosis, a library of compounds was screened for M. tuberculosis UDP-Gal mutase inhibition. Nitrofuranylamide 1 was identified as a hit in this screen, possessing good antituberculosis activity. This paper describes the synthesis and evaluation of an expanded set of nitrofuranylamides. We have discovered a number of nitrofuranylamides with submicromolar M. tuberculosis MIC values and acceptable therapeutic indexes. The MIC activity did not correlate with UDP-Gal mutase inhibition, suggesting an alternative primary cellular target was responsible for the antituberculosis activity. The compounds were only active against mycobacteria of the tuberculosis complex. On the basis of these results, four compounds were selected for in vivo testing in a mouse model of tuberculosis infection, and of these compounds one showed significant antituberculosis activity. |
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Authors:
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Rajendra P Tangallapally; Raghunandan Yendapally; Robin E Lee; Kirk Hevener; Victoria C Jones; Anne J M Lenaerts; Michael R McNeil; Yuehong Wang; Scott Franzblau; Richard E Lee |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 47 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-30 Completed Date: 2004-11-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 5276-83 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 847 Monroe Avenue, Room 327, Memphis, TN 38163, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amides
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chemical synthesis*,
chemistry,
pharmacology Animals Antitubercular Agents / chemical synthesis*, chemistry, pharmacology Databases, Factual Furans / chemical synthesis*, chemistry, pharmacology Intramolecular Transferases / antagonists & inhibitors Mice Mice, Inbred C57BL Microbial Sensitivity Tests Mycobacterium tuberculosis / drug effects* Structure-Activity Relationship Tuberculosis, Pulmonary / drug therapy |
| Grant Support | |
ID/Acronym/Agency:
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AI 053796/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amides; 0/Antitubercular Agents; 0/Furans; EC 5.4.-/Intramolecular Transferases; EC 5.4.99.9/UDP-galactopyranose mutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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