title: Comparative in vitro evaluation of N-heterocyclic carbene gold(I) complexes of the benzimidazolylidene type.
abstract: Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L=-Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.
authors: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany.
authors: Riccardo
authors: R
authors: Rubbiani
authors: Suzan
authors: S
authors: Can
authors: Igor
authors: I
authors: Kitanovic
authors: Hamed
authors: H
authors: Alborzinia
authors: Maria
authors: M
authors: Stefanopoulou
authors: Malte
authors: M
authors: Kokoschka
authors: Susann
authors: S
authors: Mönchgesang
authors: William S
authors: WS
authors: Sheldrick
authors: Stefan
authors: S
authors: Wölfl
authors: Ingo
authors: I
authors: Ott
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006046:Gold; D006801:Humans; D008024:Ligands; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056831:Coordination Complexes; D008024:Ligands; D017382:Reactive Oxygen Species; D006046:Gold; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase