Cyclometalated Iminophosphorane Gold(III) and Platinum(II) Complexes. A Highly Permeable Cationic Platinum(II) Compound with Promising Anticancer Properties

Abstract

New organometallic gold(III) and platinum(II) complexes containing iminophosphorane ligands are described. Most of them are more cytotoxic to a number of human cancer cell lines than cisplatin. Cationic Pt(II) derivatives 4 and 5, which differ only in the anion, Hg2Cl62– or PF6– respectively, display almost identical IC50 values in the sub-micromolar range (25–335-fold more active than cisplatin on these cell lines). The gold compounds induced mainly caspase-independent cell death, as previously reported for related cycloaurated compounds containing IM ligands. Cycloplatinated compounds 3, 4, and 5 can also activate alternative caspase-independent mechanisms of death. However, at short incubation times cell death seems to be mainly caspase dependent, suggesting that the main mechanism of cell death for these compounds is apoptosis. Mercury-free compound 5 does not interact with plasmid (pBR322) DNA or with calf thymus DNA. Permeability studies of 5 by two different assays, in vitro Caco-2 monolayers and a rat perfusion model, have revealed a high permeability profile for this compound (comparable to that of metoprolol or caffeine) and an estimated oral fraction absorbed of 100%, which potentially makes it a good candidate for oral administration.

Ylide Ligands as Building Blocks for Bioactive Group 11 Metal Complexes

“…Of the bis‐ylide complexes only the silver derivative 14 showed activity at the concentrations tested (<50 μ m ) but was not particularly active with an IC 50 of 48.39±2.66 μ m . It should also be noted that in these studies the complexes were incubated with the cancer cells for just 24 h and show IC 50 values far superior to cisplatin when incubated for the same period of time, but in water, which has an IC 50 value of 114.2±9.1 μ m …”

“…The silver and coppert riphenylphosphine derivatives 9 and 10 also showed excellent activityi nA 549 cells with incredibly low IC 50 values of 4.40 and 3.83 mm,r espectively.O ft he bisylide complexes only the silver derivative 14 showeda ctivity at the concentrations tested (< 50 mm)b ut was not particularly active with an IC 50 of 48.39 AE 2.66 mm.I ts hould also be noted that in theses tudies the complexes were incubated with the cancer cells for just 24 ha nd show IC 50 valuesf ar superior to cisplatin when incubated for the same period of time, but in water,which has an IC 50 value of 114.2 AE 9.1 mm. [22]…”

Gold(III) Complexes for Antitumor Applications: An Overview

“…[57] The hydrophobic/hydrophilic balance of these systemsc an easily be tuned by using am ore water-soluble phosphine such as the 1,3,5-triaza-7-phosphaadamantane (PTA). [58] (C^N^N)Au III complexes Compound 25 (Figure 8) bearing a6 -(1,1-dimethylbenzyl)-2,2'bipyridine ligand was shown to be stable toward reduction even in the presence of reductants like sodium ascorbate, while the (N^N)Au III (basedo nb ipy or phen ligands, Figure 1) were easily reduced under the same conditions. [16,59] 25 has been shownt ob eh ighly cytotoxic against A2780 ovarian cancer cells despiteaweak interaction with DNA.…”

Synthesis of functionalized biaryls using iminophosphorane palladacycles as Suzuki catalysts

“…Iminophosphoranes are ligands in coordinated compounds as well as in cyclometallated compounds with many metals, especially Au [5], Pd [6] and Pt [7], which have luminescent and anti-cancer properties. For these reasons, we have considered important to approach the synthesis of new palladium (II) cyclometallated compounds derived from iminophosphoranes and to consider their properties as Suzuki catalysts.…”