Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium

Zou, Taotao; Lok, Chun‐Nam; Wan, Pui-Ki; Zhang, Zhifeng; Fung, Sin-Ki; Che, Chi‐Ming

doi:10.1016/j.cbpa.2017.10.014

Cited by 150 publications

(69 citation statements)

References 51 publications

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“…Metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations [ 4 ]. Another advantage of metal complex therapy is their ability to mimic low-toxicity natural compounds [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

et al. 2020

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Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).

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Section: Introductionmentioning

confidence: 99%

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

et al. 2020

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“…During the past three decades, considerable attention has been given to the chemistry of metal complexes of N-heterocyclic carbenes [1][2][3][4][5][6][7][8][9]. N-heterocyclic carbenes are versatile ligands with extensive applications in coordination chemistry and catalysis, as well as in bioinorganic chemistry [10][11][12][13][14][15][16][17]. Though traditional N-heterocyclic carbenes (NHCs) are neutral "L" type ligands, NHCs bearing tethered anionic donor sites (e.g., alkoxide, aryloxide, amido etc.)…”

Section: Introductionmentioning

confidence: 99%

Mercury(II) Complexes of Anionic N-Heterocyclic Carbene Ligands: Steric Effects of the Backbone Substituent

2020

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Mercury(II) complexes (Me-maloNHCDipp)HgCl (1b), (t-Bu-maloNHCDipp)HgCl (2b) and (t-Bu-maloNHCDipp)HgMe (2c) supported by anionic N-heterocyclic carbenes have been obtained in good yields from the reaction of the potassium salt of N-heterocyclic carbene ligand precursors and mercury(II) salts, HgCl2 and MeHgI. These molecules have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. X-ray crystal structures of 1b and 2b are also presented. Interestingly, complex 1b is polymeric {(Me-maloNHCDipp)HgCl}n in the solid state, as a result of inter-molecular Hg-O contacts, and features rare three coordinate mercury sites with a T-shaped arrangement, whereas the (t-Bu-maloNHCDipp)HgCl (2b) is monomeric and has a linear, two-coordinate mercury center. The formation of T-shaped structure and the aggregation of complex 1b is attributable to the reduced steric demand of the N-heterocyclic carbene ligand backbone substituent.

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“…Due to the remarkable efficacy of metal drugs in the treatment of various cancers, the study of metal complexes has long been a hot topic [4, 5]. The metals involved in the antitumor complexes mainly include platinum-based anticancer drugs, such as cisplatin, carboplatin, and oxaliplatin [6, 7]. However, the lack of selectivity leads to the occurrence of side effects such as drug resistance, and hence their application has been greatly limited.…”

Section: Introductionmentioning

confidence: 99%

TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1

Guo

Jin

et al. 2019

Cell Commun Signal

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BackgroundIn recent years, copper complexes have gradually become the focus of potential anticancer drugs due to their available redox properties and low toxicity. In this study, a novel mitochondrion-targeting copper (II) complex, [Cu (ttpy-tpp)Br2] Br (simplified as CTB), is first synthesized by our group. CTB with tri-phenyl-phosphine (TPP), a targeting and lipophilic group, can cross the cytoplasmic and mitochondrial membranes of tumor cells. The present study aims to investigate how CTB affects mitochondrial functions and exerts its anti-tumor activity in hepatoma cells.MethodsMultiple molecular experiments including Flow cytometry, Western blot, Immunofluorescence, Tracker staining, Transmission Electron Microscopy and Molecular docking simulation were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo.ResultsCTB induced apoptosis via collapse of mitochondrial membrane potential (MMP), ROS production, Bax mitochondrial aggregation as well as cytochrome c release, indicating that CTB-induced apoptosis was associated with mitochondrial pathway in human hepatoma cells. Mechanistic study revealed that ROS-related mitochondrial translocation of p53 was involved in CTB-mediated apoptosis. Simultaneously, elevated mitochondrial Drp1 levels were also observed, and interruption of Drp1 activation played critical role in p53-dependent apoptosis. CTB also strongly suppressed the growth of liver cancer xenografts in vivo.ConclusionIn human hepatoma cells, CTB primarily induces mitochondrial dysfunction and promotes accumulation of ROS, leading to activation of Drp1. These stimulation signals accelerate mitochondrial accumulation of p53 and lead to the eventual apoptosis. Our research shows that CTB merits further evaluation as a chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).

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Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium

Cited by 150 publications

References 51 publications

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

Mercury(II) Complexes of Anionic N-Heterocyclic Carbene Ligands: Steric Effects of the Backbone Substituent

TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1

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