6WGO

The interaction of dichlorido(3-(anthracen-9-ylmethyl)-1-methylimidazol-2-ylidene)(eta6-p-cymene)ruthenium(II) with HEWL after 1 week

6WGO の概要

• エントリーDOI: 10.2210/pdb6wgo/pdb
• 分子名称: Lysozyme, SODIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: metal-based, anticancer, ruthenium, nhc, carbene, hewl, hen egg white lysozyme, lysozyme, metallodrug, imidazole, dimethylimidazole, hydrolase
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14916.56

構造登録者

Sullivan, M.P.,Hartinger, C.G.,Goldstone, D.C. (登録日: 2020-04-06, 公開日: 2021-10-06, 最終更新日: 2024-10-23)

主引用文献

Lee, B.Y.T.,Sullivan, M.P.,Yano, E.,Tong, K.K.H.,Hanif, M.,Kawakubo-Yasukochi, T.,Jamieson, S.M.F.,Soehnel, T.,Goldstone, D.C.,Hartinger, C.G.
Anthracenyl Functionalization of Half-Sandwich Carbene Complexes: In Vitro Anticancer Activity and Reactions with Biomolecules.
Inorg.Chem., 60:14636-14644, 2021

PubMed Abstract: N-Heterocyclic carbene (NHC) ligands are widely investigated in medicinal inorganic chemistry. Here, we report the preparation and characterization of a series of half-sandwich [M(L)(NHC)Cl] (M = Ru, Os, Rh, Ir; L = cym/Cp*) complexes with a N-flanking anthracenyl moiety attached to imidazole- and benzimidazole-derived NHC ligands. The anticancer activity of the complexes was investigated in cell culture studies where, in comparison to a Rh derivative with an all-carbon-donor-atom-based ligand (), they were found to be cytotoxic with IC values in the low micromolar range. The Ru derivative was chosen as a representative for stability studies as well as for biomolecule interaction experiments. It underwent partial chlorido/aqua ligand exchange in DMSO-/DO to rapidly form an equilibrium in aqueous media. The reactions of with biomolecules proceeded quickly and resulted in the formation of adducts with amino acids, DNA, and protein. Hen egg white lysozyme crystals were soaked with , and the crystallographic analysis revealed an interaction with an l-aspartic acid residue (Asp119), resulting in the cleavage of the -cymene ligand but the retention of the NHC moiety. Cell morphology studies for the Rh analog suggested that the cytotoxicity is exerted via mechanisms different from that of cisplatin.

PubMed: 34528438
DOI: 10.1021/acs.inorgchem.1c01675

実験手法

X-RAY DIFFRACTION (1.3 Å)