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Structure Activity Studies on Leaving Group Derivatives of [meso‐1,2‐Bis‐(2,6‐dichloro‐4‐hydroxyphenyl)ethylenediamine]‐platinum(II)
Author(s) -
Gust Ronald,
Keilitz Roland,
Krauser Rudolf,
Schmidt Kathrin,
Schnurr Beate
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19998)332:8<261::aid-ardp261>3.0.co;2-0
Subject(s) - chemistry , ethylenediamine , estrogen receptor , stereochemistry , moiety , estrogen , leaving group , medicinal chemistry , biochemistry , catalysis , medicine , organic chemistry , endocrinology , biology , breast cancer , cancer
The spatial structures of leaving group derivatives of [meso‐1,2‐bis(2,6‐dichloro‐4‐hydroxyphenyl)ethylenediamine]platinum(II) ( meso‐1‐PtL 2 ; L 2 = SO 4 , Cl 2 , I 2 , CBDC (cyclobutane‐1,1‐dicarboxylate)) were investigated by NMR methods and correlated with their reactivity against nucleophiles, their estrogenic potency, and their activity on the hormone dependent MCF‐7 mammary carcinoma cell line. It was demonstrated that beside the non‐leaving group meso‐1 the PtL 2 moiety of meso‐PtL 2 complexes is important for the estrogen receptor binding. Among the tested complexes meso‐1‐PtI 2 possesses the highest affinity for the estrogen receptor (RBA = 2.6) and represents a strong estrogen on the MCF‐7‐2a cell line. The use of CBDC as leaving group decreases the effects. Meso‐1‐PtCBDC shows an RBA of 0.06 and has only half of the estrogenic activity. Both complexes are sufficiently stable under physiological conditions, so a transformation into the dichloroplatinum( II) complex prior to the binding to the estrogen receptor can be excluded. Due to their high stability meso‐1‐PtI 2 and meso‐1‐ PtCBDC were only marginally active on the human estrogen receptor positive MCF‐7 cell line, while meso‐1‐PtSO 4 and meso‐1‐PtCl 2 reduced the cell growth to T/C max = 45% and 25%, respectively.