期刊
INORGANIC CHEMISTRY
卷 57, 期 4, 页码 1705-1716出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.7b01959
关键词
-
资金
- National Natural Science Foundation of China [21671118]
- Taishan Scholars Program
A series of half-sandwich Ir-III pentamethylcyclopentadienyl and Run arene complexes containing P<^>P-chelating ligands of the type [(Cp-x/arene)M(P<^>P)Cl]PF6, where M = Ir, Cp-x is pentamethylcyclopentadienyl (Cp*), or 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl (Cp-xbiPh); M = Ru, arene is 3-phenylpropan-1-ol (bz-PA), 4-phenylbutan-l-ol (bz-BA), or p-cymene (p-cym), and P<^>P is 2,20-bis(diphenylphosphino)-1,10-binaphthyl (BINAP), have been synthesized and fully characterized, three of them by X-ray crystallography, and their potential as anticancer agents explored. All five complexes showed potent anticancer activity toward HeLa and A549 cancer cells. The introduction of a biphenyl substituent on the Cp* ring for the iridium complexes has no effect on the antiproliferative potency. Ruthenium complex [(eta(6)-p-cym)Ru(P<^>P)Cl]PF6 (5) displayed the highest potency, about 15 and 7.5 times more active than the clinically used cisplatin against A549 and HeLa cells, respectively. No binding to 9-MeA and 9-EtG nucleobases was observed. Although these types of complexes interact with ctDNA, DNA appears not to be the major target. Compared to iridium complex [(eta(5)-Cp*)Ir(P<^>P)Cl]PF6 (1), ruthenium complex (5) showed stronger ability to interfere with coenzyme NAD(+)/NADH couple through transfer hydrogenation reactions and to induce ROS in cells, which is consistent with their anticancer activities. The redox properties of the complexes 1, 5, and ligand BINAP were evaluated by cyclic voltammetry. Complexes 1 and 5 arrest cell cycles at the S phase, Sub-G(1) phase and G(1), phase, respectively, and cause cell apoptosis toward A549 cells.
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