Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes

被引：13

作者：

Bestgen, Sebastian ^{[1
]}

Seidl, Carmen ^{[2
,3
]}

Wiesner, Thomas ^{[2
]}

Zimmer, Andreas ^{[2
]}

Falk, Martina ^{[2
]}

Koeberle, Beate ^{[4
]}

Austeri, Martina ^{[3
]}

Paradies, Jan ^{[5
]}

Braese, Stefan ^{[2
,3
]}

Schepers, Ute ^{[2
,3
]}

Roesky, Peter W. ^{[1
]}

机构：

[1] Karlsruhe Inst Technol, Inst Inorgan Chem, Engesserstr 15, D-76131 Karlsruhe, Germany

[2] Karlsruhe Inst Technol, Inst Toxicol & Genet, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany

[3] Karlsruhe Inst Technol, Inst Organ Chem, Fritz Haber Weg 6, D-76131 Karlsruhe, Germany

[4] Karlsruhe Inst Technol, Inst Appl Biosci, Adenauerring 20, D-76131 Karlsruhe, Germany

[5] Univ Paderborn, Inst Organ Chem, Warburger Str 100, D-33098 Paderborn, Germany

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2017年 / 23卷 / 26期

关键词：

antitumor agents; cytotoxicity; gold; paracyclophanes; phosphines; OVARIAN-CANCER CELLS; IN-VITRO; DITHIOCARBAMATE DERIVATIVES; ANTICANCER AGENTS; TUMOR-SUPPRESSOR; DEATH; AURANOFIN; CHEMISTRY; METALLOTHIONEIN; HYDROAMINATION;

D O I：

10.1002/chem.201605237

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD50 values from 3.5-38m in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (H2AX) at foci of DSBs.

引用

页码：6315 / 6322

页数：8

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