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

• Published in: European journal of medicinal chemistry 2015-08, Vol.101, p.431-441
• Main Authors: Maftei, Catalin V., Fodor, Elena, Jones, Peter G., Freytag, Matthias, Franz, M. Heiko, Kelter, Gerhard, Fiebig, Heinz-Herbert, Tamm, Matthias, Neda, Ion
• Format: Article
• Language: English
• Subjects: 1,2,4-Oxadiazoles; Animals; Anti-tumor activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bioisosters; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Gold - chemistry; Gold-NHC; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Methane - analogs & derivatives; Methane - chemistry; Methane - pharmacology; Mice; Mice, Nude; Models, Molecular; Molecular Structure; Natural product analogs; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Silver - chemistry; Silver-NHC; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2015.06.053

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