Bioactive gold and silver complexes with thiophene-conjugated amino acid esters

Abstract

Abstract Thiophene bioconjugates with methionine or tryptophan methyl esters have been prepared by reaction of chlorocarbonyl thiophene with the corresponding amino acid ester in the presence of NEt3. The coordination behaviour of these new ligands towards Ag(I) and Au(I)/Au(III) complexes has been studied. In the case of the methionine ester conjugate the coordination of the gold or silver fragments takes place through the sulfur atom of the methionine, and for the silver species [Ag(OTf)(PPh3)] coordination as HN^S chelate is proposed. For the thiophene-tryptophan ester bioconjugate the reaction with [Au(acac)(PPh2py)] (acac = acetylacetonate) results in the substitution of the proton of the cyclic NH groups by the fragment [AuPPh2py]+ affording the complex [Au(ThiopheneCOTrpOMe)(PPh2py)], whereas the reaction with no basic complexes such as [M(OTf)(PPh3)] (M = Au, Ag) produces coordination of the metal atom to the nitrogen of the indole moiety. Cytotoxicity studies towards several cancer lines such as A-549, Hep-G2 or NIH-3T3 have been performed for the tryptophan derivatives. The thiophene bioconjugate shows no activity whereas the gold and silver complexes exhibit moderate to good activities in two of the cell lines, and only the silver complex is active in the A-549 cell line.