(Pyridin-2-yl)-NHC Organoruthenium Complexes: Antiproliferative Properties and Reactivity toward Biomolecules

被引:38
作者
Movassaghi, Sanam [1 ]
Singh, Sukhjit [1 ]
Mansur, Aewan [1 ]
Tong, Kelvin K. H. [1 ]
Hanif, Muhammad [1 ]
Holtkamp, Hannah U. [1 ]
Sohnel, Tilo [1 ]
Jamieson, Stephen M. F. [2 ]
Hartinger, Christian G. [1 ]
机构
[1] Univ Auckland, Sch Chem Sci, Private Bag 92019, Auckland 1142, New Zealand
[2] Univ Auckland, Auckland Canc Soc, Res Ctr, Private Bag 92019, Auckland 1142, New Zealand
关键词
HETEROCYCLIC CARBENE COMPLEXES; CATALYTIC-ACTIVITY; TRANSFER HYDROGENATION; COUPLING REACTIONS; METAL-COMPLEXES; RUTHENIUM; LIGAND; NHC; CHEMISTRY; RHENIUM;
D O I
10.1021/acs.organomet.8b00153
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Organoruthenium compounds have been widely investigated for their anticancer activity. Here we use one of the classic ligand classes found in organometallics, i.e., N-heterocyclic carbenes (NHC), and coordinate them to the Ru(eta(6)-p-cymene) scaffold as N,C-bidentate ligands substituted with a pyridyl moiety. Introduction of different substituents gave compounds with a wide variety of properties. We investigated their stability in solution and in the presence of biomolecules, in vitro anticancer activity, and cellular uptake to rationalize their biological properties in dependence on the structure. A clear effect of their structure on the stability in water and DMSO was found for some derivatives, which was reflected in the reactivity to biomolecules that was determined with selected representatives of the compound classes. The antiproliferative activity of the compounds was widely dependent on the lipophilicity of the N,C-bidentate ligand, but as cellular accumulation studies revealed, lipophilicity does not provide the full picture and additional effects must be responsible for the anticancer activity.
引用
收藏
页码:1575 / 1584
页数:10
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