Structure activity studies on leaving group derivatives of [meso-1,2-bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]-platinum(II)

The spatial structures of leaving group derivatives of [meso-1,2-bis(2,6-di chloro-4-hydroxyphenyl)ethylenediamine]platinum(II) (meso-1-PtL2; L-2 = SO4 , Cl-2, I-2, CBDC (cyclobutane-1,1-dicarboxylate)) were investigated by NMR methods and correlated with their reactivity against nucleophiles, their e strogenic potency, and their activity on the hormone dependent MCF-7 mammar y carcinoma cell line. It was demonstrated that beside the non-leaving grou p meso-1 the PtL2 moiety of meso-PtL2 complexes is important for the estrog en receptor binding. Among the tested complexes meso-1-PtI2 possesses the h ighest affinity for the estrogen receptor for (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 hal f of the estrogenic activity. Both complexes are sufficiently stable under physiological conditions, so a transformation into the dichloroplat inum(II ) complex prior to the binding to the estrogen receptor can be excluded. Du e to their high stability meso-1-PtI2 and meso-1-PtCBDC were only marginall y active on the human estrogen receptor positive MCF-7 cell line, while mes o-1-PtSO4 acid meso-1-PtCl2 reduced the cell growth to T/C-max = 45% and 25 %, respectively.