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.
Cozzi
P
P
Department of Chemistry, Pharmacia & Upjohn, Discovery Research Oncology, Milan, Italy. paolo.cozzi@eu.pnu.com
Beria
I
I
Caldarelli
M
M
Capolongo
L
L
Geroni
C
C
Mongelli
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004214:Distamycins / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004214:Distamycins; C119510:PNU 151807