Mono and dinuclear phosphinegold(I) sulfanylcarboxylates: influence of nuclearity and substitution of PPh3 for PEt3 on cytotoxicity.

Gold complexes of the type [Au(PEt3)(Hxspa)] were prepared by reacting triethylphosphinegold(I) chloride in ethanol/water (8:1) with the 3-(aryl)-2-sulfanylpropenoic acids H2xspa [x=p=3-phenyl-; f=3-(2-furyl)-; t=3-(2-thienyl)-; py=3-(2-pyridyl); Clp=3-(2-Chlorophenyl)-; -o-mp=3-(2-methoxyphenyl)-; -p-mp=3-(4-methoxyphenyl)-; -o-hp=3-(2-hydroxyphenyl)-; -p-hp=3-(4-hydroxyphenyl)-; -diBr-o-hp=3-(3,5-dibromo-2-hidroxyphenyl-); spa=2-sulfanylpropenoato] or 2-cyclopentylidene-2-sulfanylacetic acid (H2cpa) and KOH in a 1:1:1 mole ratio. The compounds were characterized by IR spectroscopy and FAB mass spectrometry and by 1H, 13C and 31P NMR spectroscopy. The in vitro antitumor activity of these and of the previously described dinuclear [(AuPEt3)2(xspa)] complexes against the HeLa-229, A2780 and A2780cis cell lines was determined and compared with those of the analogous PPh3 complexes. The results show that the substitution of the PPh3 ligand by PEt3 is particularly effective in increasing the cytotoxicity of the dinuclear [(AuPR3)2(xspa)] complexes, giving rise to compounds that are significantly more active than cisplatin against the aforementioned cell lines. In addition, and as a preliminary test for nephrotoxicity, the cytotoxicity of the most active compounds against the normal renal LCC-PK1 cell line was evaluated and compared with that of cisplatin.