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

Abstract Gold complexes of the type [Au(PEt 3 )(H x spa)] were prepared by reacting triethylphosphinegold(I) chloride in ethanol/water (8:1) with the 3-(aryl)-2-sulfanylpropenoic acids H 2 x spa [ 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 (H 2 cpa) and KOH in a 1:1:1 mole ratio. The compounds were characterized by IR spectroscopy and FAB mass spectrometry and by 1 H, 13 C and 31 P NMR spectroscopy. The in vitro antitumor activity of these and of the previously described dinuclear [(AuPEt 3 ) 2 ( x spa)] complexes against the HeLa-229, A2780 and A2780 cis cell lines was determined and compared with those of the analogous PPh 3 complexes. The results show that the substitution of the PPh 3 ligand by PEt 3 is particularly effective in increasing the cytotoxicity of the dinuclear [(AuPR 3 ) 2 ( x spa)] 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.