Cinnamoyl nitrogen mustard derivatives of pyrazole analogues of tallimustine modified at the amidino moiety: design, synthesis, molecular modeling and antitumor activity studies

The design, synthesis and in vitro activities of a series of cinnamoyl nitrogen mustard pyrazole analogs of tallimustine 8-13, in which the amidino moiety has been replaced by moieties of different physico-chem. features are described, and the structure-activity relationships are discussed. In spite of the relevance of these modifications on the amidino moiety, these derivs. showed significant growth inhibitory activity against mouse leukemia L1210 cells. A selected series of compds. have been evaluated for their sequence selective alkylating properties and cytotoxicity against human K562 leukemia cells. Therefore, the presence of the amidino moiety, and in general of a basic moiety, is not an abs. requirement for biol. activity. Our preliminary results indicated that the compds. of this series have a pattern of alkylation similar to that of tallimustine, but they seem to be less reactive overall in alkylating naked DNA.