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

Abas, Elisa ; Espallargas, Natalia ; Burbello, Gianluca ; Mesonero, José E. (Universidad de Zaragoza) ; Rodriguez-Dieguez, Antonio ; Grasa, Laura (Universidad de Zaragoza) ; Laguna, Mariano

Resumen: New alkynylgold(I) with P(NMe2)3 (HMPT) phosphane complexes, [Au(CC-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.

Idioma: Inglés

DOI: 10.1021/acs.inorgchem.9b02528

Año: 2019

Publicado en: Inorganic Chemistry 58, 22 (2019), 15536-15551
ISSN: 0020-1669

Factor impacto JCR: 4.825 (2019)

Categ. JCR: CHEMISTRY, INORGANIC & NUCLEAR rank: 4 / 45 = 0.089 (2019) - Q1 - T1

Factor impacto SCIMAGO: 1.349 - Chemistry (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Inorganic Chemistry (Q1)

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)