Laura Capolongo

Cytotoxic halogenoacrylic derivatives of distamycin A

The design, synthesis, in vitro and in vivo activities of a series of halogenoacrylic derivatives of distamycin A are described. The structure-activity relationships indicate a key role of the reactivity of alpha-halogenoacrylic moiety. The reactivity and the putative alkylating mechanism of these compounds are different from those of the nitrogen mustards and possibly based on a Michael type reaction. This supports the hypothesis that these compounds represent a class of minor groove binders mechanistically different from tallimustine.

Novel phenyl nitrogen mustard and half-mustard derivatives of amidino-modified distamycin

Abstract The design, synthesis, and in vitro and in vivo activities of novel benzoyl and cinnamoyl nitrogen mustard and half-mustard derivatives of distamycin A, in which the amidino moiety has been replaced by moieties of different physico-chemical features, are described and structure-activity relationships are discussed. Some amidino-modified derivatives show significant cytotoxicity and antileukemic activity.

Novel phenyl nitrogen mustard and half-mustard derivatives of distamycin A

Abstract The design, synthesis, in vitro and in vivo activities of novel benzoyl and cinnamoyl nitrogen mustard and half-mustard derivatives of distamycin A are described and structure-activity relationships are discussed. The equipotent activities of N-ethyl-N-chloroethyl half-mustards and N,N-dichloroethyl mustards and the superior activities of cinnamoyl derivatives are the most relevant features of the series.

Phenyl sulfur mustard derivatives of distamycin A.

The design, synthesis, and cytotoxic activity of novel benzoyl and cinnamoyl sulfur mustard derivatives of distamycin A are described and structure activity relationships are discussed. These sulfur mustards are more potent cytotoxics than corresponding nitrogen mustards in spite of the lower alkylating power, while their sulfoxide analogues are substantially inactive. Cinnamoyl sulfur mustard derivative (7) proved to be one of the most active distamycin-derived cytotoxics, about 1000 times more potent than melphalan.

Synthesis and cytotoxic activity of alkylidene- and alkyl-substituted camptothecins

Abstract A new family of camptothecin derivatives is described. Their synthesis, in vitro cytotoxicity, and topoisomerase I inhibition is reported.