Microbial transformation of azacarbazoles. IV. Conversion of chloro-substituted alpha-carbolines by Kitasatosporia setae strain.
Biotransformation of alpha-carboline derivatives substituted at positions C-5, C-6, C-7 and C-8 with chlorine, carried out with Kitasatosporia setae strain yielded corresponding 1-methyl-alpha-iso-carbolines. The formation of products is dependent on the position of chlorine in substrate molecule. When chlorine is introduced at C-6, the yield of N-1 methylation is low, about 5%. Derivatives of alpha-carboline substituted with chlorine at C-7 and C-8 form corresponding alpha-iso-carbolines with yield up to 20% and 30%, respectively, whereas 5-chloro-alpha-carboline is converted into 5-chloro-1-methyl-alpha-iso-carboline with 60% yield. Apparently, additional pathway of microbial transformation of 2-chloro-alpha-carboline has been found. Primarily formed 2-chloro-1-methyl-alpha-iso-carboline subjected to complex enzymic conversion yields quantitatively 2-methoxy-1-methyl-alpha-iso-carboline-9-N-oxide. It has been found that 2-chloro-1-methyl-alpha-iso-carboline exhibit strong cytotoxic activity, against KB cells tissue culture, ID50 = 0.01 microM/ml and inhibits growth of Kitasatosporia setae strain, MIC = 0.5 microM/ml. Toxicity of formed 2-methoxy-1-methyl-alpha-iso-carboline-N-9-oxide is markedly lower, ID50 = 0.3 microM/ml and MIC = 3.5 microM/ml. The remaining C-5, C-6, C-7 and C-8 chloroderivatives of alpha-iso-carboline occur to be less active than 2-chloro-1-methyl-alpha-iso-carboline.
Peczyńska-Czoch
W
W
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław.
Mordarski
M
M
Kaczmarek
L
L
Nantka-Namirski
P
P
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; D008745:Methylation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002243:Carbolines; C055571:alpha-carboline