Document Detail

Growth inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium in vitro: effect of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-2'-ribofuranosyl) pyrimidine nucleoside analogs.
MedLine Citation:
PMID:  17602465     Owner:  NLM     Status:  MEDLINE    
The resurgence of tuberculosis and the emergence of multiple-drug-resistant strains of Mycobacteria necessitate the search for new classes of antimycobacterial agents. We synthesized a series of 1-beta-D-2'-arabinofuranosyl and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl) pyrimidine nucleosides possessing diverse sets of alkynyl, alkenyl, alkyl, and halo substituents at the C-5 position of the uracil and investigated their effect on activity against M. tuberculosis, M. bovis, and M. avium. Among these molecules, 5-alkynyl-substituted derivatives emerged as potent inhibitors of M. bovis, M. tuberculosis, and M. avium. Nucleosides 1-beta-D-2'-arabinofuranosyl-5-dodecynyluracil (5), 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-dodecynyluracil (24), and 1-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)-5-tetradecynyluracil (25) showed the highest antimycobacterial potency against M. bovis and M. tuberculosis. The MIC90 exhibited by compounds 5, 24, and 25 was similar or close to that of the reference drug rifampicin. The most active compounds 5, 24, and 25 were also found to retain sensitivity against a rifampicin-resistant strain of M. tuberculosis H37Rv at similar concentrations. Some of these analogs also revealed in vitro antimicrobial effect against several other gram-positive pathogens.
Monika Johar; Tracey Manning; Christopher Tse; Nancy Desroches; B Agrawal; Dennis Y Kunimoto; Rakesh Kumar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-29
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  50     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-10-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3696-705     Citation Subset:  IM    
Department of Laboratory Medicine and Pathology, 1-71 Medical Sciences Building, University of Alberta, Edmonton, AB, Canada T6G 2H7.
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MeSH Terms
Arabinofuranosyluracil / analogs & derivatives*,  chemical synthesis,  chemistry,  pharmacology
Cell Line
Cell Survival / drug effects
Cercopithecus aethiops
Drug Resistance, Bacterial
Floxuridine / analogs & derivatives*,  chemical synthesis,  chemistry,  pharmacology
Microbial Sensitivity Tests
Mycobacterium avium / drug effects*,  growth & development
Mycobacterium bovis / drug effects*,  growth & development
Mycobacterium tuberculosis / drug effects*,  growth & development
Pyrimidine Nucleosides / chemical synthesis*,  chemistry,  pharmacology
Rifampin / pharmacology
Structure-Activity Relationship
Reg. No./Substance:
0/1-(2'-deoxy-2'-fluororibofuranosyl)-5-dodecynyluracil; 0/1-(2'-deoxy-2'-fluororibofuranosyl)-5-tetradecynyluracil; 0/1-2'-arabinofuranosyl-5-dodecynyluracil; 0/Pyrimidine Nucleosides; 13292-46-1/Rifampin; 3083-77-0/Arabinofuranosyluracil; 50-91-9/Floxuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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