title: Anticancer drugs: estrophilic cisplatin derivatives.
abstract: Our approach to develop platinum complexes with a selective effect on the hormone-dependent MC by exchanging the two NH3 groups of cisplatin by an 1,2-bis(4-hydroxy-phenyl)ethylenediamine derivative which possesses estrogenic activity, was successful. The most interesting compound of this new platinum complex series, meso-(1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine)dichloroplati num(II) (meso-1-PtCl2) and its water soluble sulfatoplatinum(II) derivative (meso-1-PtSO4) were significantly more active on the DMBA-MC and the receptor positive MXT-MC than cisplatin and the related ligand 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (meso-1). According to our proposed mechanism of action, meso-1-PtX (X = Cl2 or SO4) should be enriched in the nuclei of mammary tumor cells, which possess an intact ER system (i.e. an intact cytoplasma nucleus translocation process), thereby causing very strong tumor growth inhibition. Preliminary studies of meso-1-PtSO4 on the DMBA-MC confirm this assumption. In the tumor tissue we found higher Pt-levels than in uterine tissue, which also contains ERs. The Pt-levels of the tumor tissue are much higher than those of skeletal muscle and of blood. In therapeutic dosages meso-1-PtSO4 does not cause kidney damages in rats.
authors.affiliation: Research and Development, ASTA Pharma AG, Bielefeld, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: H
authors.initials: H
authors.lastname: Schönenberger
authors.forename: F
authors.initials: F
authors.lastname: Lux
authors.forename: P
authors.initials: P
authors.lastname: Hilgard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D005260:Female; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D006589:Hexestrol; D002945:Cisplatin