کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317243 976516 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pyrophosphate-bridged complexes with picomolar toxicity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Pyrophosphate-bridged complexes with picomolar toxicity
چکیده انگلیسی

Recently, we have observed the emergence of a new series of pyrophosphate-bridged coordination complexes. Such complexes have been prepared by overcoming the ready hydrolysis of the pyrophosphate moiety. To date, no exploration has been conducted on the cytotoxicity of such complexes. Three pyrophosphate-bridged complexes, namely {[Ni(phen)2]2(μ-P2O7)}·27H2O, {[Cu(phen)(H2O)]2(μ-P2O7)}·8H2O and {[Co(phen)2]2(μ-P2O7)}·6MeOH, (where phen is 1,10′-phenanthroline) were chosen for their comparative structural similarities and suitable aqueous solubility. Cytotoxicity studies in the adriamycin-resistant ovarian cancer cell line A2780/AD demonstrated highly significant efficacy, with values as low as 160 pM for the cobalt complex at 72 h. The underlying mechanism for such exceptional toxicity is investigated focusing on DNA interactions, topoisomerase I enzyme inhibition and oxidative stress (followed by intracellular glutathione levels). The role of hydrolysis in uptake and toxicity is also explored (followed by electronic absorption spectroscopy, 31P NMR, and confocal microscopy) and the complexes are compared to cisplatin controls. Overall a clear picture of the extraordinary toxicity emerged. The results demonstrate a new class of prodrugs with significant potential for future development for the treatment of drug-resistant cancer cell lines.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 103, Issue 9, September 2009, Pages 1254–1264
نویسندگان
, , , ,