| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Monika Johar; Tracey Manning; Christopher Tse; Nancy Desroches; B Agrawal; Dennis Y Kunimoto; Rakesh Kumar |
Related Documents
:
|
9025145 - Tuberculosis in sea lions and fur seals from the south-western atlantic coast. 11377375 - Azole-antifungal binding to a novel cytochrome p450 from mycobacterium tuberculosis: im... 23190285 - Common imitators of epilepsy. 20356795 - Mycobacterium africanum is not a major cause of human tuberculosis in cape town, south ... 12825565 - Measurement and validation of the voice handicap index in voice-disordered patients in ... 22595375 - Cytogenetic evaluation: a primer for pediatric nurse practitioners. |
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 |
Affiliation:
|
Department of Laboratory Medicine and Pathology, 1-71 Medical Sciences Building, University of Alberta, Edmonton, AB, Canada T6G 2H7. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals 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 Humans 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 |
| Chemical | |
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
Previous Document: Synthesis and biological activity of a gemcitabine phosphoramidate prodrug.
Next Document: Characterization of the intracellular mechanisms involved in the antiaggregant properties of cinnamt...