A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs |
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| Authors: | Luciano Oehninger Laura Nadine Küster Claudia Schmidt Prof Dr Alvaro Muñoz‐Castro Dr med habil Dr rer nat Aram Prokop Prof Dr Ingo Ott |
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| Institution: | 1. Institute of Medicinal and Pharmaceutical Chemistry, Technische Universit?t Braunschweig, Beethovenstrasse 55, 38106 Braunschweig (Germany), Fax: (+49)?531?391?8456;2. Department of Paedriatric Oncology, Childrens Hospital Cologne, Amsterdamer Strasse 59, 50735 Cologne (Germany);3. Department of Chemical Sciences, Universidad Andres Bello, Republica 275, Santiago (Chile) |
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| Abstract: | Rhodium(I) complexes bearing N‐heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry, but there are very few reports of biological properties of these organometallics. A series of RhI‐NHC derivatives with 1,5‐cyclooctadiene and CO as secondary ligands were synthesized, characterized, and biologically investigated as prospective antitumor drug candidates. Pronounced antiproliferative effects were noted for all complexes, along with moderate inhibitory activity of thioredoxin reductase (TrxR) and efficient binding to biomolecules (DNA, albumin). Biodistribution studies showed that the presence of albumin lowered the cellular uptake and confirmed the transport of rhodium into the nuclei. Changes in the mitochondrial membrane potential (MMP) were observed as well as DNA fragmentation in wild‐type and daunorubicin‐ or vincristine‐resistant Nalm‐6 leukemia cells. Overall, these studies indicated that RhI‐NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues. |
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| Keywords: | antitumor agents carbenes cytotoxicity drug resistance rhodium thioredoxin reductase |
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