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.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Engel J,Schönenberger H,Lux F,Hilgard P

doi

10.1016/0305-7372(87)90018-1

subject

Has Abstract

pub_date

1987-12-01 00:00:00

pages

275-83

issue

3-4

eissn

0305-7372

issn

1532-1967

pii

0305-7372(87)90018-1

journal_volume

14

pub_type

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