Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 22, Issue 35, Pages 12487-12494Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201601542
Keywords
antitumor agents; carbenes; cytotoxicity; iridium; medicinal organometallic chemistry; metal-based drugs; protein interactions
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Funding
- AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro) [18044]
- COST action (STSM) [CM1105]
- Beneficentia Stiftung (Vaduz)
- CIRCMSB (Bari, Italy)
- Ruhr University Research School PLUS
- Germany's Excellence Initiative [DFG GSC 98/3]
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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 cytochromec, 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.
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