Synergetic anticancer activity of gold porphyrin appended to phenyl tin malonate organometallic complexes

Abstract

The discovery of novel anticancer chemotherapeutics is fundamental to treat cancer more efficiently. Towards this goal, two dyads consisting of a gold porphyrin appended to organotin(IV) entities were synthesized and their physicochemical and biological properties were characterized. One dyad contains a gold porphyrin connected to a tin(IV) cation via a malonate and two phenyl ligands (AuP-SnPh₂), while the other contains two tin(IV) cations each chelated to one carboxylic acid group of the malonate and three phenyl ligands (AuP-Sn₂Ph₆). The mode of chelation of Sn(IV) to the malonate was elucidated by IR spectroscopy and ¹¹⁹Sn NMR. In the solid state, the complexes exist as coordination polymers in which the tin is penta-coordinated and bridged to two different malonate units. In solution the chemical shifts of ¹¹⁹Sn signals indicate that the tin complexes are in the form of monomeric species associated with a tetra-coordinated tin cation. The therapeutic potential of these new compounds was assessed by determining their cytotoxic activities on human breast cancer cells (MCF-7) and on healthy human fibroblasts (FS 20-68). The study reveals that the dyads are more potent anticancer drugs than the mixture of their individual components (gold porphyrin and reference tin complexes). Therefore, the covalent link of organotin complexes to a gold porphyrin induces a synergistic cytotoxic effect. The dyad AuP-SnPh₂ shows high cytotoxicity (0.13 μM) against MCF-7 along with good selectivity for cancer cells versus healthy cells. Finally, it was also shown that the dyad AuP-Sn₂Ph₆ exhibits a very high anticancer activity (LC₅₀ = 0.024 μM), but the presence of two tin units induces strong cytotoxicity on healthy cells too (LC₅₀ = 0.032 μM). This study underscores, thus, the potential of the association of gold porphyrin and organotin complexes to develop anticancer metallo-drugs.