Cytotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety (original) (raw)

ÐThe design, synthesis, in vitro and in vivo activities of novel a-bromoacrylic derivatives of distamycin A, modi®ed at the amidino moiety by the replacement with basic or non-basic groups are reported. In spite of the relevance of these modi®cations of distamycin frame, the new derivatives are potent cytotoxics. The presence of the amidino moiety, is, therefore, not an absolute requirement for the activity. In particular due to a favorable myelotoxicity/cytotoxicity ratio, guanidino derivative PNU 166196 was selected for clinical development.