title: Rhodium(I) N-Heterocyclic Carbene Bioorganometallics as in Vitro Antiproliferative Agents with Distinct Effects on Cellular Signaling.
abstract: Organometallics with N-heterocyclic carbene (NHC) ligands have triggered major interest in inorganic medicinal chemistry. Complexes of the type Rh(I)(NHC)(COD)X (where X is Cl or I, COD is cyclooctadiene, and NHC is a dimethylbenzimidazolylidene) represent a promising type of new metallodrugs that have been explored by advanced biomedical methods only recently. In this work, we have synthesized and characterized several complexes of this type. As observed by mass spectrometry, these complexes remained stable over at least 3 h in aqueous solution, after which hydrolysis of the halido ligands occurred and release of the NHC ligand was evident. Effects against mitochondria and general cell tumor metabolism were noted at higher concentrations, whereas phosphorylation of HSP27, p38, ERK1/2, FAK, and p70S6K was induced substantially already at lower exposure levels. Regarding the antiproliferative activity in tumor cells, a clear preference for iodido over chlorido secondary ligands was noted, as well as effects of the substituents of the NHC ligand.
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig , Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors.forename: Luciano
authors.initials: L
authors.lastname: Oehninger
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig , Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Spreckelmeyer
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg , Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Pavlo
authors.initials: P
authors.lastname: Holenya
authors.affiliation: Department of Analytical Chemistry, University of Vienna , Waehringer Straße 38, 1090 Vienna, Austria.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Meier
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg , Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Suzan
authors.initials: S
authors.lastname: Can
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg , Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Hamed
authors.initials: H
authors.lastname: Alborzinia
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig , Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schur
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna , Waehringer Straße 42, 1090 Vienna, Austria.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg , Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig , Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D034242:Cyclooctanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D008928:Mitochondria / Q000378:metabolism; D012238:Rhodium; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D056831:Coordination Complexes; D034242:Cyclooctanes; D012238:Rhodium