Auranofin, Et3PAuCl, and Et3PAul Are Highly Cytotoxic on Colorectal Cancer Cells: A Chemical and Biological Study

被引：98

作者：

Marzo, Tiziano ^{[1
,2
]}

Cirri, Damiano ^{[2
]}

Gabbiani, Chiara ^{[1
]}

Gamberi, Tania ^{[3
]}

Magherini, Francesca ^{[3
]}

Pratesi, Alessandro ^{[2
]}

Guerri, Annalisa ^{[2
]}

Biver, Tarita ^{[1
]}

Binacchi, Francesca ^{[1
]}

Stefanini, Matteo ^{[4
]}

Arcangeli, Annarosa ^{[5
]}

Messori, Luigi ^{[2
]}

机构：

[1] Univ Pisa, Dept Chem & Ind Chem DCCI, Via Moruzzi 13, I-56124 Pisa, Italy

[2] Univ Florence, Dept Chem U Schiff, Lab Met Med MetMed, Via Lastruccia 3, I-50019 Sesto Fiorentino, Italy

[3] Univ Florence, Dept Biochem Expt & Clin Sci Mario Serio, Viale GB Morgagni 50, I-50134 Florence, Italy

[4] DIVAL Toscana SRL, Via Madonna del Piano 6, I-50019 Sesto Fiorentino, Italy

[5] Univ Florence, Dept Expt & Clin Med, Viale GB Morgagni 50, I-50134 Florence, Italy

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 10期

关键词：

Auranofin; thioredoxin reductase; anticancer drugs; colorectal cancer; protein interaction; DNA interaction; in vivo experiments; COORDINATION-COMPLEXES; GOLD; AGENT; P-31; C-13; NMR; DNA; MS;

D O I：

10.1021/acsmedchemlett.7b00162

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The solution behavior of auranofin, Et3PAuCl and Et3PAuI, as well as their interactions with hen egg white lysozyme, single strand oligonucleotide, and ds-DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement, DNA melting and viscometric tests. The cytotoxic effects toward representative colorectal cancer cell lines were found to be strong and similar in the three cases and a good correlation could be established between the cytotoxicity and the ability to inhibit thioredoxin reductase; remarkably, in vivo acute toxicity experiments for Et3PAuI confirmed that, similarly to auranofin, this drug is well tolerated in a murine model. Overall, a very similar profile emerges for Et3PAuI and Et3PAuCl, which retain the potent cytotoxic effects of auranofin while showing some peculiar features. These results demonstrate that the presence of the thiosugar moiety is not mandatory for the pharmacological action, suggesting that the tuning of some relevant chemical properties such as lipophilicity could be exploited to improve bioavailability, with no loss of the pharmacological effects.

引用

页码：997 / 1001

页数：5

共 18 条

[1] 13C, 31P and 15N NMR studies of the ligand exchange reactions of auranofin and chloro(triethylphosphine)gold (I) with thiourea [J].