Gold(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane Ligands as Thermoresponsive Anticancer Agents in Human Colon Cells

Biomedicines

Jesús Osada¹  Maria Jesús Rodriguez-Yoldi²  Francesco Ruighi³  Javier Quero³  Elena Cerrada³  M. Concepción Gimeno³ 

[1] CIBERobn, IIS Aragón, IA2, Departamento de Bioquímica y Biología Molecular, Unidad de Bioquímica, Universidad de Zaragoza, 50013 Zaragoza, Spain;CIBERobn, IIS Aragón, IA2, Departamento de Farmacología y Fisiología y Medicina Legal y Forense, Unidad de Fisiología, Universidad de Zaragoza, 50013 Zaragoza, Spain;Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, Spain;

关键词: hyperthermia;    PTA;    gold;    thiolate;    colon cancer;    TrxR;   

DOI  :  10.3390/biomedicines9121848

来源: DOAJ

【 摘 要 】

Overheating can affect solubility or lipophilicity, among other properties, of some anticancer drugs. These temperature-dependent changes can improve efficiency and selectivity of the drugs, since they may affect their bioavailability, diffusion through cell membrane or activity. One recent approach to create thermosensitive molecules is the incorporation of fluorine atoms in the chemical structure, since fluor can tune some chemical properties such as binding affinity. Herein we report the anticancer effect of gold derivatives with phosphanes derived from 1,3,5-triaza-7-phosphaadamantane (PTA) with long hydrocarbon chains and the homologous fluorinated chains. Besides, we analysed the influence of temperature in the cytotoxic effect. The studied gold(I) complexes with phosphanes derived from PTA showed antiproliferative effect on human colon carcinoma cells (Caco-2/TC7 cell line), probably by inhibiting cellular TrxR causing a dysfunction in the intracellular redox state. In addition, the cell cycle was altered by the activation of p53, and the complexes produce apoptosis through mitochondrial depolarization and the consequent activation of caspase-3. Furthermore, the results suggest that this cytotoxic effect is enhanced by hyperthermia and the presence of polyfluorinated chains.

【 授权许可】

Unknown