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将钌与二硫代氨基甲酸盐配体结合会成为肿瘤学中一种有效的化疗武器吗?

Is matching ruthenium with dithiocarbamato ligands a potent chemotherapeutic weapon in oncology?

作者信息

Nardon Chiara, Brustolin Leonardo, Fregona Dolores

机构信息

Department of Chemical Sciences, University of Padova, Via Marzolo 1, Padova, 35131, Italy.

出版信息

Future Med Chem. 2016;8(2):211-26. doi: 10.4155/fmc.15.175. Epub 2016 Jan 25.

Abstract

In the last years, several metal-based compounds have been designed and biologically investigated worldwide in order to obtain chemotherapeutics with a better toxicological profile and comparable or higher antiblastic activity than the clinically-established platinum-based drugs. In this context, researchers have addressed their attention to alternative nonplatinum derivatives able to maximize the anticancer activity of the new drugs and to minimize the side effects. Among them, a number of ruthenium complexes have been developed, including the compounds NAMI-A and KP1019, now in clinical trials. Here, we report the results collected so far for a particular class of ruthenium complexes - the ruthenium(II/III)-dithiocarbamates - which proved more potent than cisplatin in vitro, even at nanomolar concentrations, against a wide panel of human tumor cell lines.

摘要

在过去几年中,为了获得毒理学特性更佳且抗增殖活性与临床常用铂类药物相当或更高的化疗药物,全球范围内设计并对几种金属基化合物进行了生物学研究。在此背景下,研究人员将注意力转向了能够使新药的抗癌活性最大化并使副作用最小化的替代性非铂衍生物。其中,已开发出多种钌配合物,包括目前正在进行临床试验的化合物NAMI-A和KP1019。在此,我们报告了迄今为止针对一类特殊的钌配合物——二硫代氨基甲酸钌(II/III)——所收集的结果,这类配合物在体外对多种人类肿瘤细胞系的活性比顺铂更强,即使在纳摩尔浓度下也是如此。

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