Quero Javier, Royo José Carlos, Fodor Beatrice, Gimeno María Concepción, Osada Jesús, Rodríguez-Yoldi María Jesús, Cerrada Elena
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, 50009 Zaragoza, Spain.
Biomedicines. 2022 Jun 17;10(6):1437. doi: 10.3390/biomedicines10061437.
Two new families of dithiocarbamate gold(I) complexes derived from benzenesulfonamide with phosphine or carbene as ancillary ligands have been synthesized and characterized. In the screening of their in vitro activity on human colon carcinoma cells (Caco-2), we found that the more lipophilic complexes-those with the phosphine PPh-exhibited the highest anticancer activity whilst also displaying significant cancer cell selectivity. [Au(SCNHSOCH)(PPh)] () and [Au(SCNHSO-p-Me-CH)(IMePropargyl)] () produce cell death, probably by intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation, causing cell cycle arrest in the G1 phase with p53 activation. Besides this, both complexes might act as multi-target anticancer drugs, as they inhibit the activity of the enzymes thioredoxin reductase (TrxR) and carbonic anhydrase (CA IX) with the alteration of the redox balance, and show a pro-oxidant effect.
合成并表征了两个新的二硫代氨基甲酸金（I）配合物家族，它们由苯磺酰胺衍生而来，以膦或卡宾作为辅助配体。在对其对人结肠癌细胞（Caco-2）的体外活性进行筛选时，我们发现亲脂性更强的配合物——即带有膦PPh的那些配合物——表现出最高的抗癌活性，同时还显示出显著的癌细胞选择性。[Au(SCNHSOCH)(PPh)]（）和[Au(SCNHSO-p-Me-CH)(IMePropargyl)]（）导致细胞死亡，可能是通过内源性凋亡（线粒体膜电位改变）和半胱天冬酶3激活，从而在p53激活的情况下使细胞周期停滞在G1期。除此之外，这两种配合物可能作为多靶点抗癌药物发挥作用，因为它们通过改变氧化还原平衡来抑制硫氧还蛋白还原酶（TrxR）和碳酸酐酶（CA IX）的活性，并表现出促氧化作用。
