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Iridium(I) Compounds as Prospective Anticancer Agents: Solution Chemistry, Antiproliferative Profiles and Protein Interactions for a Series of Iridium(I) N‐Heterocyclic Carbene Complexes
Author(s) -
Gothe Yvonne,
Marzo Tiziano,
Messori Luigi,
MetzlerNolte Nils
Publication year - 2016
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.201601542
Subject(s) - iridium , carbene , chemistry , metalation , combinatorial chemistry , cationic polymerization , cytotoxicity , stereochemistry , in vitro , organic chemistry , biochemistry , catalysis
A series of structurally related mono‐ and bis‐NHC–iridium(I) (NHC: N‐heterocyclic carbene) complexes have been investigated for their suitability as potential anticancer drugs. Their spectral behaviour in aqueous buffers under physiological‐like conditions and their cytotoxicity against the cancer cell lines MCF‐7 and HT‐29 are reported. Notably, almost all complexes exhibit significant cytotoxic effects towards both cancer cell lines. In general, the cationic bis‐carbene complexes show higher stability and greater anticancer activity than their neutral mono‐carbene analogues with IC 50 values in the high nanomolar range. Furthermore, to gain initial mechanistic insight, the interactions of these iridium(I)–NHC complexes with two model proteins, namely lysozyme and cytochrome c, were explored by HR‐ESI‐MS analyses. The different protein metalation patterns of the complexes can be roughly classified into two distinct groups. Those interactions give us a first idea about the possible mechanism of action of this class of compounds. Overall, our findings show that iridium(I)–NHC complexes represent very interesting candidates for further development as new metal‐based anticancer drugs.