ANTHRACYCLINE MECHANISMS IN ANALOG SELECTION

  • 1 January 1985
    • journal article
    • research article
    • Vol. 11  (1) , 1-8
Abstract
Several simple test methods that revealed alterations in mechanisms of action proved to be useful in the selection of 3 new anthracycline analogs that are currently in preclinical development. 5-Iminodaunorubicin is a quinone-modified analog, and the resultant suppression of quinone redox cycling appears to correlate with diminished cardiotoxicity rather than with any effect on antitumor activity. N,N-Dibenzyldaunorubicin is an inactive prodrug requiring metabolic activation, a process that appears to give some selectivity of action leading to improved activity. The cyanomorpholino derivative of doxorubicin [3''-deamino-3''-(3-cyano-4-morpholinyl)doxorubicin] shows an intense potency against tumors that is not encountered in other closely-related analogs, indicating a highly specific mode of action as yet unidentified. Simple tests related to mechanisms of action may be more useful for analog selection than extended tests to define antitumor activity.