Antimycobacterial activity of 1-deaza-7,8-dihydropteridine derivatives against Mycobacterium tuberculosis and Mycobacterium avium complex in vitro.
Twenty-five 1-deaza-7,8-dihydropteridine derivatives were screened for antimycobacterial activity against Mycobacterium tuberculosis strain H37Ra and three Mycobacterium avium clinical isolates (serovar 1, 4 or 6). Antibacterial activity was determined with a colorimetric microdilution broth assay. Seventeen of the compounds inhibited growth in the range >1.28 to <or=12.8 mg/L against one or more of the test strains. The presence of an alkoxycarbonyl group on the amino nitrogen at position 2 was not required for activity. Activity was dependent upon the type and location of group substitutions on the 6-phenyl ring and, in some cases, the presence of a 7-alkyl group.
Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA. suling@sri.org
W J
WJ
Suling
J A
JA
Maddry
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003124:Colorimetry; D004353:Drug Evaluation, Preclinical; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011621:Pteridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D011621:Pteridines; D013762:Tetrahydrofolate Dehydrogenase