Triarylhaloethylenes as gonadotropin inhibitors

Ellipticine derivatives with an affinity to the estrogen receptor. An approach to develop intercalating drugs with a specific effect on the hormone-dependent breast cancer

“…Therefore, the binding of the nonintercalating triarylethylene ellipticine derivatives to DNA is presumably driven by external interactions of both triarylethylene and ellipticinium ion moiety. This results in rf50 values similar to that of ellipticine 19 and higher than that of clomiphene 18. This assumption is supported by the DNA intercalating ability of the composite molecule 24 in which the triarylethylene residue is replaced by a steroid moiety almost devoid of DNA affinity.…”

“…Compound 6 was prepared in four steps from 4hydroxybenzophenone (1) following the method of Palopoli et al 19 (Scheme I). Reaction of 1,2-dibromoethane with 1 gave 4-(2-bromoethoxy)benzophenone (2), which was condensed with the Grignard reagent of benzyl chloride.…”

“…Figure 5. Effect of estradiol ellipticine 24 (A, B) and ellipticine 19 (C, D) on MCF-7 cells. Cells were grown in the absence ( ) or in the presence of drug, 7 X 6 M (•), 3 X 10'6 M ( ), and 7 X 6 ( ), either in medium containing 10% fetal calf serum (A, C) or in serum free medium (B, D).…”

“…In fact, the presence of intracellular steroid-binding proteins in some tumor cells has been used more or less successfully as a basis for building tumordirected conjugates containing an (anti) estrogenic and a cytotoxic moiety. 1,13 In an attempt to obtain breast tumor directed compounds, we have connected with a spacer either a derivative of (E)-clomiphene [l-[4-[2-(diethylamino)ethoxy]phenyl]-l,2-diphenyl-2-chloroethylene, 18], a potent an-tiestrogen14 or estradiol with ellipticine (19) or ellipticine derivatives (19a,b) (see formula). Ellipticines (5,11-di-19b R = OH methyl-6ff-pyrido[4,3-c]carbazoles) are DNA intercalators and some of them, e.g., 9-hydroxyellipticine,15 show good antitumor properties.…”