Quero Javier, Alconchel Adrián, Ortega Sara, Bidooki Seyed Hesamoddin, Gimeno Mª Concepción, Rodriguez-Yoldi Mª Jesús, Cerrada Elena
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, C/ Pedro Cerbuna, 12, 50009 Zaragoza, Spain; Departamento de Farmacología y Fisiología, Unidad de Fisiología, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; Instituto de Investigaciones Sanitarias de Aragón (IIS Aragón), Instituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza (IA2), E-50013 Zaragoza, Spain; CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, E-28029 Madrid, Spain.
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, C/ Pedro Cerbuna, 12, 50009 Zaragoza, Spain.
J Inorg Biochem. 2025 Nov;272:112987. doi: 10.1016/j.jinorgbio.2025.112987. Epub 2025 Jul 7.
Mild hyperthermia has emerged as a powerful tool in cancer therapy, prompting the development of materials that respond to heat with enhanced therapeutic action. Gold(I)-NHC complexes are emerging as promising anticancer agents due to their stability, tunability, and ability to inhibit sulfur- and selenium-dependent enzymes overexpressed in tumors. In this study, we synthesised carbene-gold(I) derivatives bearing fluorous and hydrocarbon chains to assess the role of polyfluorinated groups and the impact of mild hyperthermia (41 °C) on their cytotoxic activity. The compounds exhibited significant antiproliferative effects against Caco-2/TC7 colon carcinoma cells at both 37 °C and 41 °C. This activity may be associated with alterations in the levels of ROS (reactive oxygen species) within the cells and the activity of TrxR (thioredoxin reductase), resulting in modifications to the intracellular redox state and subsequent disruptions to the cell cycle. Under hyperthermic conditions, cytotoxicity was further enhanced via mitochondrial depolarization and activation of caspase-3-mediated apoptosis. Notably, fluorinated complexes displayed superior cytotoxicity compared to their alkylated analogues, highlighting the relevance of polyfluorinated chains in boosting therapeutic efficacy under heat-triggered conditions.
轻度热疗已成为癌症治疗中的一种强大工具，促使人们开发出能通过增强治疗作用来响应热的材料。由于金（I）-氮杂环卡宾配合物具有稳定性、可调节性以及抑制肿瘤中过表达的硫和硒依赖性酶的能力，它们正成为有前景的抗癌剂。在本研究中，我们合成了带有氟代链和烃链的卡宾-金（I）衍生物，以评估多氟基团的作用以及轻度热疗（41°C）对其细胞毒性活性的影响。这些化合物在37°C和41°C时对Caco-2/TC7结肠癌细胞均表现出显著的抗增殖作用。这种活性可能与细胞内活性氧（ROS）水平的改变以及硫氧还蛋白还原酶（TrxR）的活性有关，从而导致细胞内氧化还原状态的改变以及随后对细胞周期的破坏。在热疗条件下，通过线粒体去极化和半胱天冬酶-3介导的凋亡激活，细胞毒性进一步增强。值得注意的是，与烷基化类似物相比，氟化配合物表现出更高的细胞毒性，突出了多氟链在热触发条件下提高治疗效果方面的重要性。
