Growth Inhibition of Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium In Vitro: Effect of 1-β-d -2‘-Arabinofuranosyl and 1-(2‘-Deoxy-2‘-fluoro-β-d -2‘-ribofuranosyl) Pyrimidine Nucleoside Analogs
| Autor: | Nancy Desroches, Tracey Manning, Rakesh K. Kumar, Monika Johar, Christopher Tse, Dennis Kunimoto, Babita Agrawal |
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| Rok vydání: | 2007 |
| Předmět: |
Mycobacterium bovis
Tuberculosis biology Pyrimidine medicine.drug_class biology.organism_classification medicine.disease Antimycobacterial Microbiology Mycobacterium tuberculosis chemistry.chemical_compound chemistry Drug Discovery medicine Molecular Medicine Rifampicin medicine.drug Mycobacterium Antibacterial agent |
| Zdroj: | Journal of Medicinal Chemistry. 50:3696-3705 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0703901 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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