García-Moreno Elena, Tomás Alejandro, Atrián-Blasco Elena, Gascón Sonia, Romanos Eduardo, Rodriguez-Yoldi Mary Jesus, Cerrada Elena, Laguna Mariano
Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea-ISQCH, Universidad de Zaragoza-C.S.I.C., 50009 Zaragoza, Spain.
Dalton Trans. 2016 Feb 14;45(6):2462-75. doi: 10.1039/c5dt01802a. Epub 2015 Oct 15.
Alkyne gold(I) derivatives with the water soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane) and DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) were described and their anticancer potential against the colon cancer cell line Caco-2 (PD7 and TC7 clones) was studied. Strong antiproliferative effects are found, for all the new complexes, to be even more pronounced than for the reference drug cisplatin, and similar to auranofin. The interaction of these derivatives with bovine serum albumin (BSA) was studied by fluorescence spectroscopy. The types of quenching and binding constants were determined by a fluorescence quenching method. Moderate values of the binding constants are calculated for the tested derivatives indicating that these complexes can be stored and carried easily by this protein in the body. The study of the thermodynamic parameters in the case of [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] points out to the presence of van der Waals interactions or hydrogen bonding between the metallic complex and the protein. In addition, the complex [Au(C[triple bond, length as m-dash]CCH2Spyridine)(PTA)] has shown inhibition in colon cancer proliferation of HTC-116-luc2 cell lines via the apoptotic pathway and S-phase arrest of the cell cycle. Intraperitoneal injection of this derivative in athymic nude mice inoculated with HTC-116-luc2 cells prolonged their survival and displayed moderate inhibition of the tumour growth with no subsequent organ (kidney and liver) damage after treatment.
描述了含有水溶性膦配体PTA（1,3,5 - 三氮杂 - 7 - 磷杂金刚烷）和DAPTA（3,7 - 二乙酰基 - 1,3,7 - 三氮杂 - 5 - 磷杂双环[3.3.1]壬烷）的炔基金（I）衍生物，并研究了它们对结肠癌细胞系Caco - 2（PD7和TC7克隆）的抗癌潜力。发现所有新配合物均具有很强的抗增殖作用，甚至比参比药物顺铂更显著，且与金诺芬相似。通过荧光光谱研究了这些衍生物与牛血清白蛋白（BSA）的相互作用。采用荧光猝灭法测定了猝灭类型和结合常数。计算得到的测试衍生物的结合常数适中，表明这些配合物在体内可被该蛋白质轻松储存和携带。对[Au(C≡CCH2Spyridine)(PTA)]的热力学参数研究表明，金属配合物与蛋白质之间存在范德华相互作用或氢键。此外，配合物[Au(C≡CCH2Spyridine)(PTA)]通过凋亡途径和细胞周期的S期阻滞，对HTC - 116 - luc2细胞系的结肠癌增殖表现出抑制作用。将该衍生物腹腔注射到接种了HTC - 116 - luc2细胞的无胸腺裸鼠体内，延长了它们的生存期，并对肿瘤生长表现出适度抑制，治疗后未对后续器官（肾脏和肝脏）造成损伤。
