The discovery of cisplatin made a difference in the way that chemotherapy was understood. Since then, and in order to improve the effectiveness and the clinical problems related to this kind of metallodrugs, several metals have been investigated as an alternative to this therapy. Due to the chemical similarities with Pt(II), Au(III) is a promising metal for this purpose. Nevertheless, the stabilization of this oxidation state in physiological conditions is still a difficult goal to achieve. In this research, we have studied the cyclometallation as a strategy to make stable Au(III) complexes, and we have evaluated these compounds as candidates to be used in the treatment of colon cancer. To achieve our goals, we made a huge effort to design a general strategy to obtain cycloaurated complexes, without organomercurial compounds. Thus, we have synthesized the cyclometallated Au(III) derivatives from the corresponding [AuCl3(N–CH)] complex and we have tested some ADME-tox properties of these compounds. The partition coefficient showed that, although [AuCl3(N–CH)] were more water-soluble, cyclometallated species present a better balance between hydro- and lipophilicity. That is why cycloaurated complexes were modified by the coordination of O-donor ligands and studied as anticancer drugs for colon cancer (Caco-2/TC7 cell line). The precursors ([AuCl3(N–CH)]) and starting cyclometallated complexes did not present any effect on tumour or normal cell proliferation. However, complex [Au(Phe)(ppy)]Cl presents a better antiproliferative effect than cisplatin on tumour cells and a selectivity 9-times greater towards tumour cells than towards normal cells. Some interesting conclusions actually arise from these results for a better future structural design, and thus to achieve more active anticancer drugs.

This work partially funded by Gobierno de Aragón (Spain) (Grupo Reconocido A02_17R) and associated EU Regional Developments Funds.

Peer reviewed