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Cyclometalated Gold(III) Complexes Containing N‐Heterocyclic Carbene Ligands Engage Multiple Anti‐Cancer Molecular Targets
Author(s) -
Fung Sin Ki,
Zou Taotao,
Cao Bei,
Lee PuiYan,
Fung Yi Man Eva,
Hu Di,
Lok ChunNam,
Che ChiMing
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201612583
Subject(s) - chemistry , in vivo , carbene , in vitro , cytotoxicity , cancer cell , pincer movement , combinatorial chemistry , cancer , biochemistry , stereochemistry , biology , genetics , microbiology and biotechnology , catalysis
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, Pt II and Pd II analogues 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.