Gold(I) N‐Heterocyclic Carbene Complexes with Naphthalimide Ligands as Combined Thioredoxin Reductase Inhibitors and DNA Intercalators |
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| Authors: | Andreas Meyer Dr Luciano Oehninger Dr Yvonne Geldmacher Dr Hamed Alborzinia Prof?Dr Stefan Wölfl Prof?Dr William S Sheldrick Prof?Dr Ingo Ott |
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| Affiliation: | 1. Institute of Medicinal and Pharmaceutical Chemistry, Technische Universit?t Braunschweig, Beethovenstr. 55, 38106 Braunschweig (Germany);2. Lehrstuhl für Analytische Chemie, Ruhr‐Universit?t Bochum, 44780 Bochum (Germany);3. Institute of Pharmacy and Molecular Biotechnology, Ruprecht‐Karls‐Universit?t Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg (Germany) |
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| Abstract: | 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, chlorido1‐(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. |
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| Keywords: | DNA gold naphthalimides N‐heterocyclic carbenes thioredoxin reductase |
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