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

Abstract

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; R(1) = alkylamine, R(2) = 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 an approximately 700-fold higher DNA binding than cisplatin.

Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

“…Using the commercially available butanediamine poly(propyleneimine) dendrimer (DAB(PA) 4 ) which provides four peripheral amine groups a series of tetranuclear platinum compounds were synthesised. The cationic compound [DAB(PA) 4 -{Pt(NH 3 ) 2 Cl} 4 ] 4+ was designed to overcome cisplatin resistance [30], while the neutral derivative DAB(PA) 4 {Pt(dmso)(L)} 4 (L = meso-1,2-bis(4-fluorophenyl)ethylenediamine) was prepared to increase selectivity for breast cancer cells [31].…”

Biological effect of mono- and dinuclear alkylamine platinum(II) compounds on human lymphoma cells

“…1), synthesized as described earlier [21], were dissolved in dimethylformamide (DMF, 20 mM) and stored at À20°C. Final concentrations of all compounds were prepared immediately before adding to the cultures.…”

“…To combine the selectivity of this neutral ligand with the concept of polynuclear complexes, we designed dinuclear complexes, however, with weak cytotoxic effects on human breast cancer cells [21].…”

CE in anticancer metallodrug research – an update

“…Kapp et al [49] studied the stability of the dinuclear Pt complex 14 in physiological NaCl solution, Dulbecco's buffer (containing 140 mM NaCl), and Eagle's minimal essential medium (EMEM). An exchange of the leaving DMSO ligand by a chloro ligand was determined in these media but no loss of an amine ligand was observed.…”