کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317806 1499479 2012 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: Solution behavior, reactions with model proteins, antiproliferative properties
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Gold(III) complexes with 2-substituted pyridines as experimental anticancer agents: Solution behavior, reactions with model proteins, antiproliferative properties
چکیده انگلیسی

Gold(III) compounds form a family of promising cytotoxic and potentially anticancer agents that are currently undergoing intense preclinical investigations. Four recently synthesized and characterized gold(III) derivatives of 2-substituted pyridines are evaluated here for their biological and pharmacological behavior. These include two cationic adducts with 2-pyridinyl-oxazolines, [Au(pyoxR)Cl2][PF6], [pyoxR = (S)-4-benzyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, I; (S)-4-iso-propyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, II] and two neutral complexes [Au(N,N′OH)Cl2], III, and [Au(N,N′,O)Cl], IV, containing the deprotonated ligand N-(1-hydroxy-3-iso-propyl-2-yl)pyridine-2-carboxamide, N,N′H,OH, resulting from ring opening of bound pyoxR ligand of complex II by hydroxide ions. The solution behavior of these compounds was analyzed. These behave as classical prodrugs: activation of the metal center typically takes place through release of the labile chloride ligands while the rest of the molecule is not altered; alternatively, activation may occur through gold(III) reduction. All compounds react eagerly with the model protein cyt c leading to extensive protein metalation. ESI MS experiments revealed details of gold–cyt c interactions and allowed us to establish the nature of protein bound metal containing fragments. The different behavior displayed by I and II compared to III and IV is highlighted. Remarkable cytotoxic properties, against the reference human ovarian carcinoma cell lines A2780/S and A2780/R were disclosed for all tested compounds with IC50 values ranging from 1.43 to 6.18 μM in the sensitive cell line and from 1.59 to 10.86 μM in the resistant one. The common ability of these compounds to overcome cisplatin resistance is highlighted. The obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold compounds.

Four synthesized and characterized gold(III) derivatives of 2-substituted pyridines are evaluated for their biological and pharmacological behavior. ESI MS experiments revealed details of gold–cyt c interactions and allowed to establish the nature of protein bound metal containing fragments. The common ability of compounds to overcome cisplatin resistance is highlighted.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 108, March 2012, Pages 123–127
نویسندگان
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