School of Chemistry, National University of Ireland, Galway, University Road, Galway, Ireland.
Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran.
Dalton Trans. 2017 Feb 14;46(7):2339-2349. doi: 10.1039/c6dt04339a.
A series of iridium(iii) arene complexes of naphthoquinone derivatives of the formula Ir(η-L1)(L2)(3,5-(NO)pcyd) (L1 = p-methylphenyl)ethynylferrocene; L2 = Lap: lapachol, 1, Plum: plumbagin, 2, Law: lawsone, 3, and Jug: juglone, 4; 3,5-(NO)pcyd = 3,5-dinitrophenylcyanamide) have been synthesized and investigated for their suitability as potential anticancer drugs. The DNA-binding interactions of the complexes with calf thymus DNA have been studied by absorption, emission, and viscosity measurements. Their cytotoxicity against the cancer cell lines including colon adenocarcinoma (HT-29), liver hepatocellular carcinoma (HepG-2), breast (MCF-7), colon carcinoma (HCT-8), and ovary (A2780) is reported. Remarkably, almost all complexes exhibit significant cytotoxic effects towards HepG-2, MCF-7, and HCT-8 cancer cell lines and complex 1 emerged as the most cytotoxic derivative in comparison with other complexes. The complexes 1-4 increase the production of reactive oxygen species (ROS) in MCF-7 cells. The new compounds also inhibit the enzyme thioredoxin reductase activity at nanomolar concentrations. Furthermore, the complexes induce major levels of cancer cell death by apoptosis that is in correlation with activity in cytotoxicity studies.
一系列铱(III)芳烃配合物萘醌衍生物的公式Ir(η-L1)(L2)(3,5-(NO)pcyd) (L1 = 对甲基苯基)乙炔基二茂铁; L2 = Lap: 拉帕醌, 1, Plum: 白花丹醌, 2, Law: lawsone, 3, 和 Jug: juglone, 4; 3,5-(NO)pcyd = 3,5-二硝基苯甲脒)已被合成并研究其作为潜在抗癌药物的适用性。配合物与小牛胸腺 DNA 的 DNA 结合相互作用通过吸收、发射和粘度测量进行研究。它们对包括结肠腺癌(HT-29)、肝癌(HepG-2)、乳腺癌(MCF-7)、结肠癌细胞(HCT-8)和卵巢(A2780)在内的癌细胞系的细胞毒性进行了报道。值得注意的是，几乎所有的配合物都对 HepG-2、MCF-7 和 HCT-8 癌细胞系表现出显著的细胞毒性作用，与其他配合物相比，配合物 1 表现出最强的细胞毒性。配合物 1-4 增加 MCF-7 细胞中活性氧(ROS)的产生。这些新化合物还能在纳摩尔浓度下抑制硫氧还蛋白还原酶的活性。此外，这些配合物通过细胞凋亡诱导癌细胞死亡，这与细胞毒性研究中的活性相关。
