Synthesis of gold(I) phosphine complexes containing the 2-BrC6F4PPh2 ligand: Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer cells

被引：37
|
作者：
Reddy, T. Srinivasa [1 ]
Priver, Steven H. [1 ]
Mirzadeh, Nedaossadat [1 ]
Bhargava, Suresh K. [1 ]
机构：
[1] RMIT Univ, Sch Sci, CAMIC, GPO BOX 2476, Melbourne, Vic 3001, Australia
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 145卷
关键词：
Gold(I) phosphine complexes; Anticancer activity; Spheroids; Thioredoxin reductase; Apoptosis; APOPTOSIS INDUCING AGENTS; THIOREDOXIN REDUCTASE; BIOLOGICAL EVALUATION; DERIVATIVES; INHIBITORS; DESIGN; SALTS; ASSAY;
D O I：
10.1016/j.ejmech.2017.12.048
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand have been fully characterised and their anticancer activity towards five human tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell lines investigated. Some of the synthesised gold complexes displayed higher cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the thioredoxin reductase (TrxR) enzyme, which is considered a potential target for new compounds in cancer treatment. The more physiologically relevant tumor spheroid assay demonstrated the superior potency of these gold phosphine complexes in inhibiting the growth of cervical carcinoma cell line HeLa (3D) spheroidal models. The mechanism of cell death was shown to be apoptotic cell death through cell cycle arrest, mitochondria) membrane depolarisation and increased ROS production. (C) 2017 Published by Elsevier Masson SAS.
引用
收藏
页码：291 / 301
页数：11
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