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
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
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.