Potential
Anticancer Heterometallic Fe–Au and
Fe–Pd Agents: Initial Mechanistic Insights
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Abstract
A series of gold(III) and palladium(II)
heterometallic complexes
with new iminophosphorane ligands derived from ferrocenylphosphanes
[{Cp-P(Ph<sub>2</sub>)N-Ph}<sub>2</sub>Fe] (<b>1</b>), [{Cp-P(Ph<sub>2</sub>)N-CH<sub>2</sub>-2-NC<sub>5</sub>H<sub>4</sub>}<sub>2</sub>Fe] (<b>2</b>), and [{Cp-P(Ph<sub>2</sub>)N-CH<sub>2</sub>-2-NC<sub>5</sub>H<sub>4</sub>}Fe(Cp)]
(<b>3</b>) have been synthesized and structurally characterized.
Ligands <b>2</b> and <b>3</b> afford stable coordination
complexes [AuCl<sub>2</sub>(<b>3</b>)]ClO<sub>4</sub>, [{AuCl<sub>2</sub>}<sub>2</sub>(<b>2</b>)](ClO<sub>4</sub>)<sub>2</sub>, [PdCl<sub>2</sub>(<b>3</b>)], and [{PdCl<sub>2</sub>}<sub>2</sub>(<b>2</b>)]. The complexes have been evaluated for their
antiproliferative properties in human ovarian cancer cells sensitive
and resistant to cisplatin (A2780S/R), in human breast cancer cells
(MCF7) and in a nontumorigenic human embryonic kidney cell line (HEK-293T).
The highly cytotoxic trimetallic derivatives M<sub>2</sub>Fe (M =
Au, Pd) are more cytotoxic to cancer cells than their corresponding
monometallic fragments. Moreover, these complexes were significantly
more cytotoxic than cisplatin in the resistant A2780R and the MCF7
cell lines. Studies of the interactions of the trimetallic compounds
with DNA and the zinc-finger protein PARP-1 indicate that they exert
anticancer effects in vitro based on different mechanisms of actions
with respect to cisplatin
