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-a...

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Veröffentlicht in:Journal of medicinal chemistry 1985-06, Vol.28 (6), p.752-761
Hauptverfasser: Delbarre, Alain, Oberlin, Robert, Roques, Bernard P, Borgna, Jean Louis, Rochefort, Henri, Le Pecq, Jean Bernard, Jacquemin-Sablon, Alain
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00383a011