Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights

Abstract

A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenyl-phosphanes [{Cp-P(Ph2)=N-Ph}2Fe] (1), [{Cp-P(Ph2)=N-CH2-2-NC5H4}2Fe] (2) and [{Cp-P(Ph2)=N-CH2-2-NC5H4}Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl2(3)]ClO4, [{AuCl2}2(2)](ClO4)2, [PdCl2(3)] and [{PdCl2}2(2)]. The complexes have been evaluated for their antripoliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M2Fe (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.

Synthesis, structures, antiproliferative activity of a series of ruthenium(II) arene derivatives of thiosemicarbazones ligands

“…HSA, which is the most abundant carrier protein in plasma, can bind a variety of substrates such as metal cations, hormones, and most therapeutic drugs [22]. The combination of complexes with HSA can enhance their stability in the bloodstream and bioavailability at target tissues.…”

Synthesis, physical and antimicrobial studies of ferrocenyl-N-(pyridinylmethylene)anilines and ferrocenyl-N-(pyridinylmethyl)anilines

“…The ferrocenylpyridine metalloligands have been employed in coordination of other metals yielding bimetallic systems with excellent anti-cancer potencies comparable to the drug cisplatin, courtesy of the synergistic effect between the two active metals. 21,33,34 Also, ferrocenylpyridine Schiff bases have been found to show broadspectrum biological activity against pathogenic microbes.…”

Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate

“…3,4 Nonetheless, side effects combined with limited pharmacokinetic properties remain significant drawbacks. 5−7 Therefore, there is a growing demand for overcoming toxicity and efficacy issues.…”