Antitumor Activity of Gold(I), Silver(I) and Copper(I) ComplexesContaining Chiral Tertiary Phosphines

Abstract

Abstract.The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC50 values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino)ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)-and (R*,R*)-l,2-phenylenebis(methylphenylphosphine); and (R,R )-, (S,S)-and (R*, R')-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CHlcisR and SKOV-3 tumour models. IC5o values in the range 0.01 0.04 #M were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC50 data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand.Introduction.

The induction of cell death by phosphine silver(I) thiocyanate complexes in SNO-esophageal cancer cells

“…Viability studies to assess toxicity of compounds Different Ag(I) phosphine complexes have shown to target a wide range of malignancies (Berners-Price and Sadler 1988;McKeage et al 1998;Liu et al 2008;Zartilas et al 2009;Kyros et al 2010;Poyraz et al 2011;Kriel and Coates 2012;Goita et al 2013;Banti et al 2014;Yilmaz et al 2014). Therefore, the cell death-inducing abilities of complexes 1-4 were examined in SNO-esophageal cancer cells.…”

“…Specifically, Ag(I) tertiary phosphine adducts showed remarkable anticancer activity against a panel of ovarian cancer cell lines including a P815 melanoma cell line with IC 50 values ranging from 0.012 to 0.52 lM. Interestingly, this complex was more effective than the Au(I) analog, with an IC 50 between 0.15 and 0.55 lM (McKeage et al 1998). In another study, two tetrahedral Ag(I) triphenylphosphine complexes with incorporated salicylic acid and o-hydroxybenzoic acid, respectively, showed anticancer activity in rat leiomyosarcoma cells (LMS) and human breast cancer cells (MCF-7) at low micromolar concentrations.…”

“…Berners-Price and Sadler (1988) proposed that silver(I) [Ag(I)] phosphine complexes exhibit anticancer properties in cell lines, but the antimicrobial activity outperformed it. Currently, Ag(I) has shown toxic activity in a wide range of tumor and cancer cell models (McKeage et al 1998;Liu et al 2008;Kyros et al 2010;Poyraz et al 2011;Kriel and Coates 2012;Goita et al 2013;Banti et al 2014;Yilmaz et al 2014). Specifically, Ag(I) tertiary phosphine adducts showed remarkable anticancer activity against a panel of ovarian cancer cell lines including a P815 melanoma cell line with IC 50 values ranging from 0.012 to 0.52 lM.…”

“…Lipophilic Au(I) and Ag(I) bidentate pyridylphosphine complexes have shown to contain improved anticancer properties in cisplatin-resistant CH1, 41M, SKOV-3, CH1-cisR and 41M-cisR human ovarian carcinoma cell-lines (Liu et al 2008). Overall, Ag(I) phosphine death targeting mechanisms are not fully understood, although certain studies suggest mitochondrial action in cancer cells (McKeage et al 1998;Kriel and Coates 2012) and yeast models (Berners-Price et al 1994, 1995.…”

Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studies

“…106 Gold phosphine compounds containing a variable number of coordinated phosphorus atoms (from 1 to 4) show increased cytotoxic potency in murine tumor cell lines as the number of gold-coordinated phosphorus atoms increases. 107,108 Unfortunately, after relatively encouraging studies on selected tumor cell lines, [109][110][111][112] auranofin analogues containing thiolate ligands derived from thionucleobases (phosphine gold(I) thionucleobase compounds) have not demonstrated marked cytotoxic activity when screened through the National Cancer Institute's panel of 60 tumor cell lines. 113 However, related phosphine gold(I) thiolates show higher cytotoxic activity compared with cisplatin and 5-fluorouracil in seven human solid tumor cell lines.…”