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Guided Antitumoural Drugs: (Imidazol‐2‐ylidene)(L)gold(I) Complexes Seeking Cellular Targets Controlled by the Nature of Ligand L
Author(s) -
Bär Sofia I.,
Gold Madeleine,
Schleser Sebastian W.,
Rehm Tobias,
Bär Alexander,
Köhler Leonhard,
Carnell Lucas R.,
Biersack Bernhard,
Schobert Rainer
Publication year - 2021
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.202005451
Subject(s) - thioredoxin reductase , ligand (biochemistry) , chemistry , carbene , cytotoxicity , cancer cell , stereochemistry , apoptosis , reactive oxygen species , nucleus , mitochondrion , in vitro , biochemistry , medicinal chemistry , receptor , thioredoxin , cancer , enzyme , microbiology and biotechnology , biology , genetics , catalysis
Three [1,3‐diethyl‐4‐( p ‐methoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)imidazol‐2‐ylidene](L)gold(I) complexes, 4 a (L=Cl), 5 a (L=PPh 3 ), and 6 a (L=same N‐heterocyclic carbene (NHC)), and their fluorescent [4‐(anthracen‐9‐yl)‐1,3‐diethyl‐5‐phenylimidazol‐2‐ylidene](L)gold(I) analogues, 4 b , 5 b , and 6 b , respectively, were studied for their localisation and effects in cancer cells. Despite their identical NHC ligands, the last three accumulated in different compartments of melanoma cells, namely, the nucleus ( 4 b ), mitochondria ( 5 b ), or lysosomes ( 6 b ). Ligand L was also more decisive for the site of accumulation than the NHC ligand because the couples 4 a / 4 b , 5 a / 5 b , and 6 a / 6 b , carrying different NHC ligands, afforded similar results in cytotoxicity tests, and tests on targets typically found at their sites of accumulation, such as DNA in nuclei, reactive oxygen species and thioredoxin reductase in mitochondria, and lysosomal membranes. Regardless of the site of accumulation, cancer cell apoptosis was eventually induced. The concept of guiding a bioactive complex fragment to a particular subcellular target by secondary ligand L could reduce unwanted side effects.