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Gold(I) N ‐Heterocyclic Carbene Complexes with Naphthalimide Ligands as Combined Thioredoxin Reductase Inhibitors and DNA Intercalators
Author(s) -
Meyer Andreas,
Oehninger Luciano,
Geldmacher Yvonne,
Alborzinia Hamed,
Wölfl Stefan,
Sheldrick William S.,
Ott Ingo
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402049
Subject(s) - thioredoxin reductase , moiety , chemistry , carbene , stereochemistry , reductase , combinatorial chemistry , dna , enzyme , cytotoxic t cell , intercalation (chemistry) , ribonucleotide reductase , biochemistry , thioredoxin , in vitro , organic chemistry , protein subunit , gene , catalysis
Organometallic conjugates consisting of a gold(I) N ‐heterocyclic carbene (NHC) moiety and a naphthalimide were prepared and investigated as cytotoxic agents that interact with both DNA and the disulfide reductase enzyme thioredoxin reductase (TrxR). The complexes were potent DNA intercalators related to their naphthalimide partial structure, inhibited TrxR as a consequence of the incorporation of the gold(I) moiety, and triggered efficient cytotoxic effects in MCF‐7 breast and HT‐29 colon adenocarcinoma cells. Strong effects on tumor cell metabolism were noted for the most cytotoxic complex, chlorido[1‐(3′‐(4′′‐ethylthio‐1′′,8′′‐naphthalimid‐ N ′′‐yl))‐propyl‐3‐methyl‐imidazol‐2‐ylidene]gold(I) ( 4 d ). In conclusion, the conjugation of naphthalimides with gold(I) NHC moieties provided a useful strategy for the design of bioorganometallic anticancer agents with multiple modes of action.