Porchia Marina, Pellei Maura, Marinelli Marika, Tisato Francesco, Del Bello Fabio, Santini Carlo
CNR-ICMATE, Corso Stati Uniti, 4, 35127 Padova, Italy.
School of Science and Technology, Chemistry Division, University of Camerino, via S. Agostino 1, 62032 Camerino, Macerata, Italy.
Eur J Med Chem. 2018 Feb 25;146:709-746. doi: 10.1016/j.ejmech.2018.01.065. Epub 2018 Jan 31.
Within the research field of antitumor metal-based agents alternative to platinum drugs, gold(I/III) coordination complexes have always been in the forefront due mainly to the familiarity of medicinal chemists with gold compounds, whose application in medicine goes back in the ancient times, and to the rich chemistry shown by this metal. In the last decade, N-heterocyclic carbene ligands (NHC), a class of ligands that largely resembles the chemical properties of phosphines, became of interest for gold(I) medicinal applications, and since then, the research on NHC-gold(I/III) coordination complexes as potential antiproliferative agents boosted dramatically. Different classes of gold(I/III)-NHC complexes often showed an outstanding in vitro antiproliferative activity, however up to now very few in vivo data have been reported to corroborate the in vitro results. This review summarizes all achievements in the field of gold (I/III) complexes comprising NHC ligands proposed as potential antiproliferative agents in the period 2004-2016, and critically analyses biological data (mainly IC values) in relation to the chemical structures of Au compounds. The state of art of the in vivo studies so far described is also reported.
在作为铂类药物替代物的抗肿瘤金属基药物研究领域,金(I/III)配位络合物一直处于前沿位置,这主要归因于药物化学家对金化合物的熟悉程度(金化合物在医学上的应用可追溯到古代)以及该金属所展现出的丰富化学性质。在过去十年中,N-杂环卡宾配体(NHC),这一类在很大程度上类似于膦化学性质的配体,引起了金(I)药物应用领域的关注,从那时起,对作为潜在抗增殖剂的NHC-金(I/III)配位络合物的研究急剧增加。不同类别的金(I/III)-NHC络合物通常表现出出色的体外抗增殖活性,然而截至目前,仅有极少的体内数据被报道以证实体外研究结果。本综述总结了2004年至2016年期间在金(I/III)络合物领域所取得的全部成果,这些络合物包含被提议作为潜在抗增殖剂的NHC配体,并批判性地分析了与金化合物化学结构相关的生物学数据(主要是IC值)。同时还报道了迄今为止所描述的体内研究的现状。