A new anthracycline with potent antileukemic activity exhibits reduced mutagenicity.
The mutagenicity of a new anthracycline (moflomycin) with potent antileukemic activity was studied by the Ames test in four strains of Salmonella typhimurium (TA97a, TA98, TA100 and TA102), and compared to the mutagenicity of doxorubicin, widely used as antineoplastic agent. Unlike doxorubicin, moflomycin displayed no mutagenic activity in strains TA98 and TA100. Low mutagenicity was only observed in TA102 strain and was not enhanced after metabolic activation. This result indicates that moflomycin induce mutagenicity by reverting base-pair substitution. The structural changes in the sugar moiety may be involved in the reduced mutagenicity of moflomycin. The low mutagenicity of moflomycin shown in this study enhances the potential advantage of this new derivative which displays a high antileukemic activity.
D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D001711:Biotransformation; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D007938:Leukemia / Q000188:drug therapy*; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D009153:Mutagens; C063104:moflomycin; D004317:Doxorubicin; D003630:Daunorubicin