A chemical-biological evaluation of rhodium(I) N-heterocyclic carbene complexes as prospective anticancer drugs.
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 Rh(I)-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 Rh(I)-NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues.
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig (Germany), Fax: (+49) 531 391 8456.
Luciano
L
Oehninger
Laura Nadine
LN
Küster
Claudia
C
Schmidt
Alvaro
A
Muñoz-Castro
Aram
A
Prokop
Ingo
I
Ott
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; C030011:carbene; D012238:Rhodium; D008697:Methane
antitumor agents; carbenes; cytotoxicity; drug resistance; rhodium; thioredoxin reductase