Conjugates of ferrocene with biological compounds. Coordination to gold complexes and antitumoral properties

Several bioconjugates of ferrocene with biological compounds such as aminoacid esters and related species have been prepared by reaction of chlorocarbonyl ferrocene with the corresponding amino acid ester (histidine methyl ester, tryptophan methyl ester, methionine methyl ester and lysine ethyl ester) or histamine or prolinamide in the presence of NEt3. The reaction of the tryptophan or prolinamide ferrocene conjugates with [Au(acac)(PR3)] (acac = acetylacetonate) results in the substitution of the proton of the cyclic NH groups by the fragment AuPR3+ affording the complexes [Au(FcCO-tryptophan-OMe)(PR3)] or [Au(FcCO-prolinamide)(PR3)] (Fc = ferrocenyl group). The reaction of FcCO-Met-OMe with [Au(OTf)(PR3)] (OTF = trifluoromethysulfonate) or [Au(C6F5)3(OEt2)] yields the gold(I) or gold(III) derivatives [Au(FcCO-Met-OMe)(PR3)]OTf or [Au(C6F5)3(FcCO-Met-OMe)], respectively. Cytotoxicity studies towards several cancer lines such as MCF-7, HeLa or NIE-115 have been performed. The ferrocene bioconjugates show no activity whereas the gold complexes exhibit antiproliferative effect. Preliminary studies of interaction of compounds with cells were carried out with the goal of increasing our knowledge on the mechanism of action of these potential drugs.

Graphical abstractA family of new complexes associating conjugates of ferrocene with aminoacid esters to Au(I) or Au(III) metal centers was designed and synthesized aiming at improving the biological properties of each type of compound. The antitumor properties of some of these gold complexes toward two human and one murine cancer cell lines have been investigated showing good activities.Figure optionsDownload full-size imageDownload as PowerPoint slide