کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1318040 976635 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Terpyridine–platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Terpyridine–platinum(II) complexes are effective inhibitors of mammalian topoisomerases and human thioredoxin reductase 1
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 103, Issue 7, July 2009, Pages 1082–1092
نویسندگان
, , , , ,