Design, synthesis and evaluation of estradiol-linked genotoxicants as anticancer agents

A series of bifunctional compounds was prepared consisting of 17β estradiol linked to a DNA damaging N,N-bis (2-chloroethyl)-aniline. The objective of our studies was to detem1ine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor.