Development of Cytotoxic GW7604-Zeise's Salt Conjugates as Multitarget Compounds with Selectivity for Estrogen Receptor- Positive Tumor Cells.

()-3-(4-(()-1-(4-Hydroxyphenyl)-2-phenylbut-1-enyl)phenyl)acrylic acid () as a carrier was esterified with alkenols of various lengths and coordinated through the ethylene moiety to PtCl, similar to Zeise's salt (K[PtCl(CH)]). The resulting complexes (Alk = Prop, But, Pent, Hex) degraded in aqueous solution only by exchange of the chlorido ligands. For example, coordinated the amino acid alanine in the cell culture medium, bound the isolated nucleotide 5'-GMP, and interacted with the DNA (empty plasmid pSport1). It accumulated in estrogen receptor (ER)-positive MCF-7 cells primarily cytosolic vesicles, while it was only marginally taken up in ER-negative SKBr3 cells. Accordingly, and related complexes were inactive in SKBr3 cells. showed high affinity to ERα and ERβ without mediating agonistic or ER downregulating properties. ligands also increased the cyclooxygenase (COX)-2 inhibitory potency of the complexes. In contrast to Zeise's salt, the complexes inhibited COX-1 and COX-2 to the same extent.