Microbial transformation of azacarbazoles. VII. Antitumor properties of benzo-alpha-iso-carbolines formed by Kitasatosporia setae strain from corresponding benzo-alpha-carbolines.
2,3-Benzo-alpha-carboline, 7,8-benzo-alpha-carboline and their 4-methyl derivatives were subjected to microbial conversion yielding corresponding benzo-alpha-iso-carbolines. All obtained products showed significant antimicrobial and cytotoxic properties. ID50 values were found to be at range 0.01-0.001 microM/ml, regarding in vitro KB tumor cells system data. It has been found that introduction of methyl group at para-position to the nitrogen of pyridine nucleus strongly increases cytotoxic and microbial activity of benzo-alpha-iso-carbolines. Apparently it has been indicated that antitumor activity of benzo-alpha-iso-carbolines is strongly dependent on shape and size of the molecule. Of all the compounds tested only 2,3-benzo-1,4-dimethyl-alpha-iso-carboline increases life span of leukemia P388 bearing mice up to 160%.
Peczyńska-Czoch
W
W
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
D000192:Actinomycetales / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D002243:Carbolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D008745:Methylation; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002243:Carbolines