Microbial transformation of azacarbazoles. III. Conversion of methoxy- and phenyl- substituted alpha-carbolines to corresponding alpha-iso-carbolines by Kitasatosporia setae strain.
Microbial N-1 methylation of alpha-carboline derivatives substituted at position C-2, C-6 and C-8 with methoxy- and at position C-2 and C-6 with phenyl groups conducted with Kitasatosporia setae resulted in corresponding alpha-iso-carboline formation. The yield of obtained products is significantly dependent on the position of substituent in alpha-carboline molecule. Compounds, as 2- and 6-methoxy-alpha-carboline undergo N-1 microbial methylation with strikingly low yields of 5%, whereas products of biotransformation of 8-methoxy-alpha-carboline was formed in markedly higher amount, about 50%. Similar correlations were observed for subjected to bioconversion C-2 and C-6 phenyl-alpha-carbolines. The yields of formed products were estimated as 3% and 5%, respectively. All obtained alpha-iso-carbolines were found to be toxic to the transforming strain of Kitasatosporia setae at the range of 1.2-2.5 microM/ml as well as against KB tumor culture cells (ID50 0.04-0.6 microM/ml).
Peczyńska-Czoch
W
W
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
D000192:Actinomycetales / Q000187:drug effects / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001711:Biotransformation; D002243:Carbolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002243:Carbolines; C055571:alpha-carboline