赫拉
化学
顺铂
HT1080型
三苯基膦
细胞毒性
体内
癌症研究
细胞凋亡
血管生成
立体化学
纤维肉瘤
体外
生物化学
化疗
内科学
病理
生物
催化作用
生物技术
医学
作者
T. Srinivasa Reddy,Steven H. Privér,Nedaossadat Mirzadeh,Rodney B. Luwor,Velma Ganga Reddy,Shwathy Ramesan,Suresh K. Bhargava
出处
期刊:Inorganic Chemistry
[American Chemical Society]
日期:2020-04-07
卷期号:59 (8): 5662-5673
被引量:22
标识
DOI:10.1021/acs.inorgchem.0c00423
摘要
A family of stable anticancer gold(III)-based therapeutic complexes containing cyclometalated triphenylphosphine sulfide ligands have been prepared. The anticancer properties of the newly developed complexes [AuCl2{κ2-2-C6H4P(S)Ph2}] (1), [Au(κ2-S2CNEt2){κ2-2-C6H4P(S)Ph2}]PF6 (2), [AuCl(dppe){κC-2-C6H4P(S)Ph2}]Cl (3), and [Au(dppe){κ2-2-C6H4P(S)Ph2}][PF6]2 (4) were investigated toward five human cancer cell lines [cervical (HeLa), lung (A549), prostate (PC3), fibrosarcoma (HT1080), and breast (MDA-MB-231)]. In vitro cytotoxicity studies revealed that compounds 2–4 displayed potent cell growth inhibition (IC50 values in the range of 0.17–2.50 μM), comparable to, or better than, clinically used cisplatin (0.63–6.35 μM). Preliminary mechanistic studies using HeLa cells indicate that the cytotoxic effects of the compounds involve apoptosis induction through ROS accumulation. Compound 2 also demonstrated significant inhibition of endothelial cell migration and tube formation in the angiogenesis process. Evaluation of the in vivo antitumor activity of compound 2 in nude mice bearing cervical cancer cell (HeLa) xenografts indicated significant tumor growth inhibition (55%) with 1 mg/kg dose (every 3 days) compared with the same dose of cisplatin (28%). These results demonstrate the potential of gold(III) complexes containing cyclometalated triphenylphosphine sulfide ligands as novel metal-based anticancer agents.
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