Title |
Gold(I)–NHC complexes of antitumoral diarylimidazoles: Structures, cellular uptake routes and anticancer activities
|
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Published in |
Journal of Inorganic Biochemistry, September 2011
|
DOI | 10.1016/j.jinorgbio.2011.08.026 |
Pubmed ID | |
Authors |
Leonard Kaps, Bernhard Biersack, Helge Müller-Bunz, Katharina Mahal, Julienne Münzner, Matthias Tacke, Thomas Mueller, Rainer Schobert |
Abstract |
Five new heterocyclic gold carbene complexes were prepared, four chlorido-[1,3-dimethyl-4,5-diarylimidazol-2-ylidene]gold complexes 6a-d and a chlorido-[1,3-dibenzylimidazol-2-ylidene]gold complex 11, and three of them were characterised by X-ray single crystal analyses. They were tested for cytotoxicity against a panel of four human cancer cell lines and non-malignant fibroblasts, for tubulin interaction, and for the pathways of their uptake into 518A2 melanoma cells. All complexes showed cytotoxic activity in the micromolar IC(50) range with distinct selectivities for certain cell lines. In stark contrast to related metal-free 1-methyl-4,5-diarylimidazoles, the complexes 6 and 11 did not noticeably inhibit the polymerisation of tubulin to give microtubules. The cellular uptake of complexes 6 occurred mainly via the copper transporter (Ctr1) and the organic cation transporters (OCT-1/2). Complex 11 was accumulated preferentially via the organic cation transporters and by Na(+)/K(+)-dependent endocytosis. The new gold carbene complexes seem to operate by a mechanism different from that of the parent 1-methylimidazolium ligands. |
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Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
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Unknown | 50 | 96% |
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Student > Ph. D. Student | 13 | 25% |
Student > Master | 9 | 17% |
Researcher | 7 | 13% |
Student > Bachelor | 6 | 12% |
Student > Doctoral Student | 3 | 6% |
Other | 7 | 13% |
Unknown | 7 | 13% |
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Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
Other | 2 | 4% |
Unknown | 9 | 17% |