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抗癌有机金属锇(II)-对异丙基苯配合物

Anticancer Organometallic Osmium(II)-p-cymene Complexes.

作者信息

Păunescu Emilia, Nowak-Sliwinska Patrycja, Clavel Catherine M, Scopelliti Rosario, Griffioen Arjan W, Dyson Paul J

机构信息

Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne (Switzerland).

Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam (The Netherlands).

出版信息

ChemMedChem. 2015 Sep;10(9):1539-47. doi: 10.1002/cmdc.201500221. Epub 2015 Jul 14.

Abstract

Osmium compounds are attracting increasing attention as potential anticancer drugs. In this context, a series of bifunctional organometallic osmium(II)-p-cymene complexes functionalized with alkyl or perfluoroalkyl groups were prepared and screened for their antiproliferative activity. Three compounds from the series display selectivity toward cancer cells, with moderate cytotoxicity observed against human ovarian carcinoma (A2780) cells, whereas no cytotoxicity was observed on non-cancerous human embryonic kidney (HEK-293) cells and human endothelial (ECRF24) cells. Two of these three cancer-cell-selective compounds induce cell death largely via apoptosis and were also found to disrupt vascularization in the chicken embryo chorioallantoic membrane (CAM) model. Based on these promising properties, these compounds have potential clinical applications.

摘要

锇化合物作为潜在的抗癌药物正受到越来越多的关注。在此背景下,制备了一系列用烷基或全氟烷基官能化的双功能有机金属锇(II)-对异丙基苯配合物,并对其抗增殖活性进行了筛选。该系列中的三种化合物对癌细胞具有选择性,对人卵巢癌(A2780)细胞观察到中等细胞毒性,而对非癌性人胚肾(HEK-293)细胞和人内皮(ECRF24)细胞未观察到细胞毒性。这三种癌细胞选择性化合物中的两种主要通过凋亡诱导细胞死亡,并且还发现在鸡胚绒毛尿囊膜(CAM)模型中破坏血管生成。基于这些有前景的特性,这些化合物具有潜在的临床应用价值。

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