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Mono- and Polynuclear [Alkylamine]platinum(II) Complexes of [1,2-Bis(4-fluorophenyl)ethylenediamine]platinum(II):  Synthesis and Investigations on Cytotoxicity, Cellular Distribution, and DNA and Protein Binding

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journal contribution
posted on 09.02.2006, 00:00 by Timo Kapp, Anja Dullin, Ronald Gust
A series of mononuclear and dinuclear alkylamine derivatives of [meso-1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) (m-4F-PtL-R1 and (m-4F-PtL)2-R2; R1 = alkylamine, R2 = alkyldiamine, L = DMSO or Cl) as well as the DAB(PA)4 polyimine dendrimer complex ((m-4F-PtDMSO)4DAB(PA)4; DAB(PA)4 = N,N,N‘,N‘-tetrakis(3-aminopropyl)butane-1,4-diamine) were synthesized and tested for cytotoxicity, intracellular distribution, and DNA and protein binding. All compounds strongly bound to human serum albumin by hydrophobic and electrostatic interactions. These inactivation reactions hindered the uptake into tumor cells and prevented strong cytotoxic effects. If serum-free medium was used, a high accumulation grade in MCF-7 breast cancer cells and a high DNA binding was observed. As most efficient compound (m-4F-PtDMSO)4DAB(PA)4 was identified. It showed a 20-fold higher cellular uptake and a ∼700-fold higher DNA binding than cisplatin.