Anticancer Activity of Alkynylgold(I) with P(NMe2)3 Phosphane in Mouse Colon Tumors and Human Colon Carcinoma Caco-2 Cell Line.

Abstract

New alkynylgold(I) with P(NMe2)3 (HMPT) phosphane complexes, [Au(C≡C-R)(HMPT)] (R= 4-Ph, 4-MePh, 4-OMe, 4-Br, 4-Cl, 2-py, and 3-py) have been synthesized and characterized, including X-ray studies of complexes with R= 4-OMe and 4-Br; additionally, their physicochemical properties and anticancer activity have been tested. Due to the great water solubility of the HMPT phosphane, all the complexes exhibit an optimal balance of hydrophilicity/lipophilicity. Also, all of these complexes are quite stable in physiological conditions and interact well enough with the transport protein BSA. All complexes exhibit a higher anticancer activity against Caco-2 cells than cisplatin, and some of them do not present cytotoxic activity against enterocyte-like differentiated cells. The selective complexes are proapoptotic drugs by the exposure of phosphatidylserine, results that are also confirmed in primary cultures from mouse colon tumors. Complexes with a halogen unit also arrest the cell cycle in G2/M phase. It is thought that maybe these apoptosis processes are promoted by the observed oxidative damage in the membrane lipids, as a consequence of the inhibition of the thioredoxin reductase enzyme. Based on our results, we conclude that five of our complexes are good candidates to be used in chemotherapy.