Simpson Peter V, Casari Ilaria, Paternoster Silvano, Skelton Brian W, Falasca Marco, Massi Massimiliano
Curtin Institute of Functional Molecules and Interfaces, Department of Chemistry, Curtin University, Kent Street, Bentley, 6102 WA, Australia.
Metabolic Signalling Group, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, 6102, Australia.
Chemistry. 2017 May 11;23(27):6518-6521. doi: 10.1002/chem.201701208. Epub 2017 Apr 12.
Rhenium and ruthenium complexes containing N-heterocylic carbene (NHC) ligands and conjugated to indomethacin were prepared. The anticancer properties were probed against pancreatic cell lines, revealing a remarkable activity of the rhenium fragment as anticancer agent. The ruthenium complexes were found to be inactive against the same pancreatic cancer cell lines, either alone or in conjugation with indomethacin. An in-depth biological study revealed the origin of the anticancer properties of the rhenium tricarbonyl fragment, of which a complete elucidation had yet to be achieved. It was found that the rhenium complexes induce cell cycle arrest at the G2/M phase by inhibiting the phosphorylation of Aurora-A kinase. A preliminary study on the structure-activity relationship on a large family of these complexes revealed that the anticancer properties are mainly associated with the lability of the ancillary ligand, with inert complexes showing limited to no anticancer properties.
制备了含有N-杂环卡宾（NHC）配体并与吲哚美辛共轭的铼和钌配合物。对胰腺癌细胞系研究了其抗癌特性，结果表明铼片段作为抗癌剂具有显著活性。发现钌配合物单独或与吲哚美辛共轭时，对相同的胰腺癌细胞系均无活性。深入的生物学研究揭示了三羰基铼片段抗癌特性的来源，对此尚未完全阐明。研究发现铼配合物通过抑制极光激酶A（Aurora-A kinase）的磷酸化诱导细胞周期停滞于G2/M期。对这类配合物大家族的构效关系进行的初步研究表明，抗癌特性主要与辅助配体的不稳定性有关，惰性配合物显示出有限的抗癌特性或无抗癌特性。
