Gold(I) complexes bearing alkylated 1, 3, 5-triaza-7-phosphaadamantane ligands as thermoresponsive anticancer agents in human colon cells

Quero J. ; Ruighi F. ; Osada J. (Universidad de Zaragoza) ; Gimeno M.C. ; Cerrada E. (Universidad de Zaragoza) ; Rodriguez-Yoldi M.J. (Universidad de Zaragoza)

Resumen: Overheating can affect solubility or lipophilicity, among other properties, of some an-ticancer 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Idioma: Inglés

DOI: 10.3390/biomedicines9121848

Año: 2021

Publicado en: Biomedicines 9, 12 (2021), 1848
ISSN: 2227-9059

Factor impacto JCR: 4.757 (2021)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 121 / 297 = 0.407 (2021) - Q2 - T2
Categ. JCR: PHARMACOLOGY & PHARMACY rank: 87 / 279 = 0.312 (2021) - Q2 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 62 / 140 = 0.443 (2021) - Q2 - T2

Factor impacto CITESCORE: 3.0 - Medicine (Q2) - Biochemistry, Genetics and Molecular Biology (Q3)

Factor impacto SCIMAGO: 0.874 - Medicine (miscellaneous) (Q1) - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/B16-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MICINN-ISCIIII-FEDER/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-104379RB-C21

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)