Anticancer activity of Ru- and Os(arene) compounds of a maleimide-functionalized bioactive pyridinecarbothioamide ligand

被引：38

作者：

Hanif, Muhammad ^{[1
]}

Moon, Sally ^{[1
]}

Sullivan, Matthew P. ^{[1
,2
]}

Movassaghi, Sanam ^{[1
]}

Kubanik, Mario ^{[1
]}

Goldstone, David C. ^{[2
]}

Sohnel, Tilo ^{[1
]}

Jamieson, Stephen M. F. ^{[3
]}

Hartinger, Christian G. ^{[1
]}

机构：

[1] Univ Auckland, Sch Chem Sci, Private Bag 92019, Auckland 1142, New Zealand

[2] Univ Auckland, Sch Biol Sci, Private Bag 92019, Auckland 1142, New Zealand

[3] Univ Auckland, Auckland Canc Soc, Res Ctr, Private Bag 92019, Auckland 1142, New Zealand

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2016年 / 165卷

基金：

美国国家卫生研究院; 奥地利科学基金会;

关键词：

Ru(arene) complexes; Anticancer agents; Bioorganometallics; Albumin carrier; Maleimide; HUMAN SERUM; COMPLEXES; DRUG; RUTHENIUM; ALBUMIN; SELECTIVITY; PLATFORM; CANCER;

D O I：

10.1016/j.jinorgbio.2016.06.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

With the aim of increasing the accumulation of Ru anticancer agents in the tumor, a targeted delivery strategy based on a maleimide anchor for the biological vector human serum albumin (HSA) was developed. A group of piano stool Ru-and Os(eta(6)-arene) complexes carrying a maleimide-functionalized N-phenyl-2pyridinecarbothioamide (PCA) ligand was designed allowing for covalent conjugation to biological thiols. The complexes were characterized by NMR spectroscopy, ESI-MS, elemental analysis and single -crystal X-ray diffraction analysis. The compounds were shown to undergo halido/aqua ligand exchange reactions in aqueous solution, depending mainly on the metal center and the nature of the halide. In vitro cytotoxicity studies revealed low potency which is explained by the observed high reactivity of the maleimide to the thiol of t-cysteine (Cys), while the metal center itself shows little affinity to amino acids of the model protein lysozyme. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：100 / 107

页数：8

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