title: N-heterocyclic carbenes (NHC) with 1,2,4-oxadiazole-substituents related to natural products: synthesis, structure and potential antitumor activity of some corresponding gold(I) and silver(I) complexes.
abstract: This work presents the synthesis, characterization and application of eleven new gold (I) complexes 13-23 with 1,2,4-oxadiazole-containing N-heterocyclic carbene (NHC) ligands and of the NHC silver(I) complex 24. The 1,2,4-oxadiazole unit, which can be found in a variety of biologically active natural products such as phidianidines or quisqualic acid, was incorporated, along with a variety of other biologically active moieties (anthracene, indole, 2-pyridine, 2,3,4,5-tetra-O-acetyl-D-glucopyranose, quincorine and quincoridine), in order to change the lipophilicity of the complexes, so that the transport of the active units (M-NHC) though the cell wall barrier is facilitated. The biological activity of the complexes was investigated. In vitro assessment of anti-tumor activity in a panel of 12 human tumor cell lines by a monolayer assay revealed impressive potency (mean IC50 < 0.1 μM) and tumor selectivity for 6 compounds, with individual IC50 values in the low nanomolar range. The solid state structures of compounds 13, 14, 15, 17, 18, 19 and 24 were determined by X-ray diffraction analyses.
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany; Institutul National de Cercetare Dezvoltare pentru Electrochimie si Materie Condensata, Str. Dr. A. Paunescu Podeanu, Nr. 144, Ro-300569 Timisoara, Romania.
authors.forename: Catalin V
authors.initials: CV
authors.lastname: Maftei
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany; Institutul National de Cercetare Dezvoltare pentru Electrochimie si Materie Condensata, Str. Dr. A. Paunescu Podeanu, Nr. 144, Ro-300569 Timisoara, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Fodor
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Jones
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Freytag
authors.affiliation: InnoChemTech GmbH, Hagenring 30, D-38106 Braunschweig, Germany; Institutul National de Cercetare Dezvoltare pentru Electrochimie si Materie Condensata, Str. Dr. A. Paunescu Podeanu, Nr. 144, Ro-300569 Timisoara, Romania.
authors.forename: M Heiko
authors.initials: MH
authors.lastname: Franz
authors.affiliation: Oncotest GmbH, Am Flughafen 12-14, D-79108 Freiburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.affiliation: Oncotest GmbH, Am Flughafen 12-14, D-79108 Freiburg, Germany.
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany. Electronic address: m.tamm@tu-bs.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Tamm
authors.affiliation: Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany; Institutul National de Cercetare Dezvoltare pentru Electrochimie si Materie Condensata, Str. Dr. A. Paunescu Podeanu, Nr. 144, Ro-300569 Timisoara, Romania. Electronic address: i.neda@tu-bs.de.
authors.forename: Ion
authors.initials: I
authors.lastname: Neda
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D012834:Silver / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010069:Oxadiazoles; C030011:carbene; D012834:Silver; D006046:Gold; D008697:Methane
keywords: 1,2,4-Oxadiazoles; Anti-tumor activity; Bioisosters; Gold-NHC; Natural product analogs; Silver-NHC