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.
In order to obtain breast tumor directed agents, we have prepared mixed compounds using estradiol or (E)-clomiphene as specific vectors of the breast tissue and a DNA intercalator from the ellipticine series as the cytotoxic agent. Among the newly synthesized ellipticine derivatives, only the 2-[3-aza-5-(3,17 beta-dihydroxy-1,3,5-estratrien-17 alpha-yl)-4-oxopentamethylene]ellipticinium bromide shows the desired properties, DNA intercalation and affinity for estrogen receptor. Competition experiments with estradiol on the hormone-dependent human MCF-7 breast cancer cell line demonstrate that a transport by the estrogen receptor system is not involved in the antitumor activity of derivative 24.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004611:Ellipticines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011960:Receptors, Estrogen / Q000378:metabolism*
D000470:Alkaloids; D004611:Ellipticines; D007364:Intercalating Agents; D011960:Receptors, Estrogen; D004247:DNA