title: A multi-target caffeine derived rhodium(i) N-heterocyclic carbene complex: evaluation of the mechanism of action.
abstract: A rhodium(i) and a ruthenium(ii) complex with a caffeine derived N-heterocyclic carbene (NHC) ligand were biologically investigated as organometallic conjugates consisting of a metal center and a naturally occurring moiety. While the ruthenium(ii) complex was largely inactive, the rhodium(i) NHC complex displayed selective cytotoxicity and significant anti-metastatic and in vivo anti-vascular activities and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor. In HCT-116 cells it increased the reactive oxygen species level, leading to DNA damage, and it induced cell cycle arrest, decreased the mitochondrial membrane potential, and triggered apoptosis. This rhodium(i) NHC derivative thus represents a multi-target compound with promising anti-cancer potential.
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, D-38106 Braunschweig, Germany. ingo.ott@tu-bs.de and Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Department of Organic Chemistry, University Bayreuth, Universitätsstr. 30, D-95440 Bayreuth, Germany.
authors.forename: Julienne K
authors.initials: JK
authors.lastname: Muenzner
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abu El Maaty
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research GmbH, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Karge
authors.affiliation: Department of Organic Chemistry, University Bayreuth, Universitätsstr. 30, D-95440 Bayreuth, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
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, Beethovenstr. 55, D-38106 Braunschweig, Germany. ingo.ott@tu-bs.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D002110:Caffeine / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012238:Rhodium / Q000737:chemistry / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D056831:Coordination Complexes; D017382:Reactive Oxygen Species; C030011:carbene; D002110:Caffeine; D012238:Rhodium; D008697:Methane