Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1

Yan Chung Lo, Tzu Ping Ko, Wen Chi Su, Tsann Long Su, Andrew H.J. Wang

研究成果: 雜誌貢獻文章同行評審

90 引文 斯高帕斯(Scopus)

摘要

Terpyridine-platinum(II) (TP-Pt(II)) complexes are known to possess DNA-intercalating activity and have been regarded as potential antitumor agents. However, their cytotoxic mechanism remains unclear. To investigate the possible mechanism, a series of TP-Pt(II) compounds were prepared and their biological activities assessed. The DNA binding activities of the aromatic thiolato[TP-Pt(II)] complexes were stronger than the aliphatic 2-hydroxylethanethiolato(2,2′:6′,2′′-terpyridine)platinum(II) [TP(HET)]. TP-Pt(II) complexes inhibited topoisomerase IIα or topoisomerase I activity at IC50 values of about 5 μM and 10-20 μM, respectively, whereas the human thioredoxin reductase 1 (hTrxR1) activity was inhibited with IC50 values in the range of 58-78 nM. At the cellular level, they possessed cytotoxicity with IC50 values between 7 and 19 μM against HeLa cells. Additionally, using X-ray crystallography and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, we elucidated that the TP-Pt(II) complexes inhibited hTrxR1 activity by blocking its C-terminal active-site selenocysteine. Therefore, TP-Pt(II) complexes possess inhibitory activities against multiple biological targets, and they may be further studied as anticancer agents.

原文英語
頁(從 - 到)1082-1092
頁數11
期刊Journal of Inorganic Biochemistry
103
發行號7
DOIs
出版狀態已發佈 - 7月 2009
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 無機化學

指紋

深入研究「Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1」主題。共同形成了獨特的指紋。

引用此