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).