Ruthenium(II) p-cymene complexes of naphthoquinone derivatives as antitumor agents: A structure-activity relationship study

被引：26
作者：
Tabrizi, Leila [1 ]
Chiniforoshan, Hossein [1 ]
机构：
[1] Isfahan Univ Technol, Dept Chem, Esfahan 8415683111, Iran
来源：
JOURNAL OF ORGANOMETALLIC CHEMISTRY | 2016年 / 822卷
关键词：
Ru(II) complex; Naphthoquinone; Cytotoxicity; Hypoxia; Apoptosis; IN-VITRO; THIOREDOXIN REDUCTASE; ANTICANCER ACTIVITY; ARENE COMPLEXES; PROTEIN-BINDING; CELL-LINES; DNA; LIGAND; CYTOTOXICITY; EXPRESSION;
D O I：
10.1016/j.jorganchem.2016.09.003
中图分类号：
O61 [无机化学];
学科分类号：
070301 ; 081704 ;
摘要：
Four ruthenium(II) p-cymene complexes of Naphthoquinone Derivatives of formula [Ru-II(eta(6)-p-cymene) (Lap) (PTA)](PF6), 1, [RuII(eta(6)-p-cymene) (Plum) (PTA)](PF6), 2, [Ru-II(eta(6)-p-cymene) (Law) (PTA)](PF6), 3, [Ru-II(eta(6)-p-cymene) (Jug) (PTA)](PF6), 4 (Lap: lapachol, Plum: plumbagin, Law: lawsone, Jug: juglone, PTA: 1,3,5-triaza-7-phosphaadamantane) have been synthesized and fully characterized. The complexes 1-4 revealed a significant in vitro antiproliferative activity against human melanoma (A375), liver hepatocellular carcinoma (HepG-2), breast (MCF-7), colon adenocarcinoma (LoVo), ovary (A2780) and colon carcinoma (HCT-8) cancer cell lines. Complexes were active under hypoxic conditions. The enzyme thioredoxin reductase is overexpressed in cancer cells, and complexes inhibit this enzyme, with IC50 values measured in the nanomolar range. Moreover, the complexes induce major levels of cancer cell death by apoptosis that is in correlation with activity in cytotoxicity studies. Comparative release of lactate dehydrogenase (LDH) and cellular accumulation of the Ru(II) complexes 1-4 have also been carried out. (C) 2016 Elsevier B.V. All rights reserved.
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页码：211 / 220
页数：10
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