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A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and Bioconjugated Complexes: Synthesis and Anticancer Potential
Author(s) -
Bertrand Benoît,
O'Connell Maria A.,
Waller Zoë A. E.,
Bochmann Manfred
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705902
Subject(s) - bimetallic strip , chemistry , linker , cancer cell , estrogen receptor , ligand (biochemistry) , combinatorial chemistry , in vitro , conjugate , pincer movement , carbene , receptor , biophysics , cancer , biochemistry , metal , breast cancer , biology , organic chemistry , mathematical analysis , mathematics , computer science , catalysis , genetics , operating system
Cyclometalated (C^N^C)Au III complexes bearing functionalized N‐heterocyclic carbene (NHC) ligands provide a high‐yielding, modular route to bioconjugated and binuclear complexes. This methodology has been applied to the synthesis of bioconjugated complexes presenting biotin and 17α‐ethynylestradiol vectors, as well as to the synthesis of bimetallic Au III /Au I complexes. The in vitro antiproliferative activities of these compounds against various cancer cells lines depend on the linker length, with the longer linker being the most potent. The estradiol conjugate AuC 6 Estra proved to be more toxic against the estrogen receptor positive (ER+) cancer cells than against the ER− cancer cells and non‐cancer cells. The bimetallic complex AuC 6 Au was more selective for breast cancer cells with respect to a healthy cell standard than the monometallic complex AuNHC . The metal uptake study on cells expressing or not biotin and estrogen receptors revealed an improved and targeted delivery of gold for both the bioconjugated complexes AuC 6 Biot and AuC 6 Estra compared to the non‐vectorised analogue AuNHC . The investigations of the interaction of the bioconjugates and bimetallic complexes with human telomeric G‐quadruplex DNA using FRET‐melting techniques revealed a reduced ability to stabilize this DNA structure with respect to the non‐vectorised analogue AuNHC .