title: Cyclometalated Gold(III) Complexes Containing N-Heterocyclic Carbene Ligands Engage Multiple Anti-Cancer Molecular Targets.
abstract: Metal N-heterocyclic carbene (NHC) complexes are a promising class of anti-cancer agents displaying potent in vitro and in vivo activities. Taking a multi-faceted approach employing two clickable photoaffinity probes, herein we report the identification of multiple molecular targets for anti-cancer active pincer gold(III) NHC complexes. These complexes display potent and selective cytotoxicity against cultured cancer cells and in vivo anti-tumor activities in mice bearing xenografts of human cervical and lung cancers. Our experiments revealed the specific engagement of the gold(III) complexes with multiple cellular targets, including HSP60, vimentin, nucleophosmin, and YB-1, accompanied by expected downstream mechanisms of action. Additionally, PtIIand PdIIanalogues can also bind the cellular proteins targeted by the gold(III) complexes, uncovering a distinct pincer cyclometalated metal-NHC scaffold in the design of anti-cancer metal medicines with multiple molecular targets.
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Sin Ki
authors.initials: SK
authors.lastname: Fung
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Yi Man Eva
authors.initials: YM
authors.lastname: Fung
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Chun-Nam
authors.initials: CN
authors.lastname: Lok
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials, Chemical Biology Centre and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.|HKU Shenzhen Institute of Research and Innovation, Shenzhen, 518053, China.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D050607:Organogold Compounds / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D050607:Organogold Compounds; C030011:carbene; D008697:Methane
keywords: N-heterocyclic carbene; anti-cancer mechanisms; gold; metal medicines; target identification