Microbial transformation of azacarbazoles. II. Conversion of methyl-substituted alpha-carbolines to corresponding alpha-iso-carbolines by Kitasatosporia setae strain.
alpha-Carboline derivatives substituted with methyl groups at C-2, C-4, C-2,4, C-6 and C-8 position were subjected to N-1 methylation performed by Kitasatosporia setae. The yield of formed corresponding alpha-iso-carbolines varied, depending on the position of methyl substituent. It has been observed that the methyl group introduced in position C-2 and C-6 of alpha-carboline molecule markedly diminishes the susceptibility of nitrogen for enzymic attack in comparison with methylation reaction performed with methyl iodide. On the contrary, derivatives possessing methyl groups in positions C-4 and C-8 are methylated by chemical and microbial means with approximately the same yield. The obtained alpha-iso-carbolines appeared to be toxic to the transforming Kitasatosporia setae strain at the concentration range of 0.2-2.5 microM/ml. Taking into account that the MIC values of parent alpha-carbolines estimated for Kitasatosporia setae were much higher than 2.5 microM/ml, this finding seems to be out of the accordance with the general belief that the microbial conversion of xenobiotics is only a detoxification process. Apparently, 4-methyl and 2 -dimethyl substituted alpha-iso-carbolines besides of their antimicrobial properties, displayed strong cytotoxic activity against KB cells line at the concentration range 0.03-0.05 microM/ml.
Peczyńska-Czoch
W
W
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
D000192:Actinomycetales / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001711:Biotransformation; D002243:Carbolines / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002621:Chemistry; D008745:Methylation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002243:Carbolines; C055571:alpha-carboline