title: Iridium(I) Compounds as Prospective Anticancer Agents: Solution Chemistry, Antiproliferative Profiles and Protein Interactions for a Series of Iridium(I) N-Heterocyclic Carbene Complexes.
abstract: 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 IC50 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.
authors.affiliation: Inorganic Chemistry I-Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, 44801, Bochum, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gothe
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.|Department of Chemistry and Industrial Chemistry (DCCI), University of Pisa, Via Moruzzi 13, 56124, Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Marzo
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Inorganic Chemistry I-Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, 44801, Bochum, Germany. Nils.Metzler-Nolte@rub.de.
authors.forename: Nils
authors.identifier: http://orcid.org/0000-0001-8111-9959
authors.initials: N
authors.lastname: Metzler-Nolte
keywords: antitumor agents; carbenes; cytotoxicity; iridium; medicinal organometallic chemistry; metal-based drugs; protein interactions