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

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Dec 24

PMID 34944664

Citations 5

Authors

Javier Quero

Francesco Ruighi

Jesus Osada

M Concepcion Gimeno

Elena Cerrada

Maria Jesus Rodriguez-Yoldi

Affiliations

Soon will be listed here.

Abstract

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.

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