Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides.
Mycobacterium tuberculosis and Mycobacterium avium infections cause the two most important mycobacterioses, leading to increased mortality in patients with AIDS. Various 5-substituted 2'-deoxyuridines, uridines, 2'-O-methyluridine, 2'-ribofluoro-2'-deoxyuridines, 3'-substituted-2',3'-dideoxy uridines, 2',3'-dideoxyuridines, and 2',3'-didehydro-2',3'-dideoxyuridines were synthesized and evaluated for their in vitro inhibitory activity against M. bovis and M. avium. 5-(C-1 Substituted)-2'-deoxyuridine derivatives emerged as potent inhibitors of M. avium (MIC90 = 1-5 microg/mL range). The nature of C-5 substituents in the 2'-deoxyuridine series appeared to be a determinant of anti-mycobacterial activity. This new class of inhibitors could serve as useful compounds for the design and study of new anti-tuberculosis agents.
Johar
Monika
M
Department of Laboratory Medicine and Pathology, 1-71 Medical Sciences Building, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Manning
Tracey
T
Kunimoto
Dennis Y
DY
Kumar
Rakesh
R
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009162:Mycobacterium avium / Q000187:drug effects; D009163:Mycobacterium bovis / Q000187:drug effects; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D011741:Pyrimidine Nucleosides