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Synthesis and Mode of Action Studies on Iridium(I)–NHC Anticancer Drug Candidates
Author(s) -
Gothe Yvonne,
RomeroCanelón Isolda,
Marzo Tiziano,
Sadler Peter J.,
Messori Luigi,
MetzlerNolte Nils
Publication year - 2018
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201800225
Subject(s) - chemistry , carbene , iridium , thiazole , cationic polymerization , stereochemistry , reactive oxygen species , iodide , mesoionic , medicinal chemistry , biological activity , organic chemistry , in vitro , biochemistry , catalysis
We report the synthesis, characterization, and biological activity of Ir I complexes with triazole‐ (NNHC) and thiazole‐based (NSHC) N‐heterocyclic carbene ligands. Starting from the dimeric [Ir(COD)Cl] 2 , we obtained complexes of composition Ir(COD)(NNHC)Cl ( 4a ), Ir(COD)(NNHC)X ( 4b : X = Cl; 4bBr : X = Br), [Ir(COD)(NNHC)(NHC)]I ( 5a ), [Ir(COD)(NSHC) 2 ]Cl ( 6a ), and [Ir(COD)(NSHC)(NNHC)]Cl ( 6b ) by adaptation of established synthetic methods for metal–NHC complexes. Their interactions with model proteins cytochrome c and lysozyme, as well as with the oligonucleotide hexamer (CG) 3 (ODN1), were studied. Although most complexes did not show any strong interactions with these biomolecules, all complexes were active against HT‐29 and MCF‐7 cancerous cells, with IC 50 values ranging between 1 and 60 µ m . The most active compounds were the cationic bis(carbene) derivatives 5 and 6 . All compounds generated high levels of reactive oxygen species (ROS) after incubation for 48 h in MCF‐7 cells, possibly suggesting a redox‐mediated mechanism of action. Interestingly, there were distinctive differences in the superoxide/(total ROS) ratios induced by the different groups of compounds.