HENYL)-2-PHENYLETHYLENEDIAMINE]SULFATOPLATINUM(II) COMPLEXES WITH VARIABLE SUBSTITUENTS IN THE 2-PHENYL RING .2. CORRELATION OF MOLECULAR-STRUCTURE AND ESTROGENIC ACTIVITY OF BREAST AND PROSTATE-CANCER INHIBITING -HALO-4-HYDROXYPHENYL)ETHYLENEDIAMINE]PLATINUM(II) COMPLEXES

Citation
R. Gust et al., HENYL)-2-PHENYLETHYLENEDIAMINE]SULFATOPLATINUM(II) COMPLEXES WITH VARIABLE SUBSTITUENTS IN THE 2-PHENYL RING .2. CORRELATION OF MOLECULAR-STRUCTURE AND ESTROGENIC ACTIVITY OF BREAST AND PROSTATE-CANCER INHIBITING -HALO-4-HYDROXYPHENYL)ETHYLENEDIAMINE]PLATINUM(II) COMPLEXES, Archiv der pharmazie, 326(12), 1993, pp. 967-976
Citations number
49
Categorie Soggetti
Chemistry,"Pharmacology & Pharmacy
Journal title
ISSN journal
03656233
Volume
326
Issue
12
Year of publication
1993
Pages
967 - 976
Database
ISI
SICI code
0365-6233(1993)326:12<967:HCWV>2.0.ZU;2-5
Abstract
Complete three-dimensional X-ray crystal structure analyses of estroge nic 4-hydroxyphenyl)ethylenediamine]diiodoplatinum(II) complexes (halo = fluoro:erythro-8-PtI2 and halo = chloro:erythro-9-PtI2) which were synthesized for application in breast and prostate cancer, have been c arried out. 6239 as well as 6521 reflexes were measured and refined to an R-value of 0.105 and 0.066, respectively. The molecules of erythro -8-PtI2 are displaced laterally from a possible Pt-Pt-axis separated, alternatingly, by Pt-Pt-distances of 3.62 Angstrom A and 6.27 Angstrom A. a comparable structure possesses erythro-9-PtI2 with Pt-Pt-distanc es of 3.59 Angstrom A and 6.32 Angstrom A. the ethylenediamine ligands of erythro-8-PtI2 and erythro-9-PtI2 are puckered and exist in half c hair conformations. For both complexes the 2,6-dichloro-4- hydroxyphen yl ring is equatorially arranged, while the 2-halo-4-hydroxyphenyl rin g is nearly perpendicular to the N-Pt-N plane. The O-O-distance betwee n the phenolic oxygens amounts to 8.1 Angstrom A in erythro-8-PtI2 and to 7.8 Angstrom A in erythro-9-PtI2. Though these O-O-distances diffe r strongly from that (12.1 Angstrom A), which is considered to be nece ssary for the binding of an estrogen to its receptor, halo-4-hydroxyph enyl)ethylenediamine)]platinum(II) complexes show estrogenic effects w hich are, however, strongly reduced compared to that of therapeuticall y used estrogens like diethylstilbestrol. The relationship between mol ecular structure and estrogenicity as well as the significance of the latter for antitumor activity and untoward side effects ate thoroughly discussed.