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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 IIalpha or topoisomerase I activity at IC(50) values of about 5 microM and 10-20 microM, respectively, whereas the human thioredoxin reductase 1 (hTrxR1) activity was inhibited with IC(50) values in the range of 58-78 nM. At the cellular level, they possessed cytotoxicity with IC(50) values between 7 and 19 microM 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.

Terpyridine-platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1., Lo YC, Ko TP, Su WC, Su TL, Wang AH, J Inorg Biochem. 2009 Jul;103(7):1082-92. Epub 2009 May 21. PMID:19525010

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Categories: Homo sapiens | Thioredoxin-disulfide reductase | Ko, T P. | Lo, Y C. | Wang, A H.J. | Alternative splicing | Cytoplasm | Electron transport | Fad | Flavoprotein | Nadp | Nucleus | Oxidoreductase | Phosphoprotein | Polymorphism | Redox-active center | Rossmann fold | Selenium | Selenocysteine | Transport