Recent outcome in the field of distamycin-derived minor groove binders.
DNA minor groove binders represent a class of cytotoxic antitumor agents whose DNA sequence specificity may lead to a high selectivity of action. Tallimustine, benzoyl nitrogen mustard derivative of distamycin A, showed excellent antitumor activity in the preclinical tests, but as other minor groove binders, showed severe myelotoxicity. Novel nitrogen mustard derivatives of distamycin showing improved activity profile, have been identified recently. Moreover, a series of alpha-halogenoacrylamido derivatives of distamycin-like frames, in which the typical amidino moiety has been replaced with other moieties, was found to show cytotoxic and antitumor activity and cytotoxicity/myelotoxicity ratio improved significantly in comparison to tallimustine. The structural features of the alkylating moieties and binding frames, of distamycin and distamycin-like derivatives disclosed recently are discussed.
Department of Chemistry, Pharmacia & Upjohn, Nerviano, Milan, Italy. paolo.cozzi@eu.pnu.com
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D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000494:pharmacology; D004214:Distamycins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008466:Mechlorethamine / Q000138:chemical synthesis / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*
D018906:Antineoplastic Agents, Alkylating; D004214:Distamycins; D019384:Nucleic Acid Synthesis Inhibitors; D008466:Mechlorethamine