Organogold(III) compounds as experimental anticancer agents: chemical and biological profiles
| Autor: | Chiara Gabbiani, Damiano Cirri, Lara Massai, Elena Michelucci, Maria Agostina Cinellu, Annalisa Guerri, Fabio Cocco, Gianluca Bartoli, Luigi Messori |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular RNase P Metalation Stereochemistry Electrospray ionization Pharmacology toxicology Antineoplastic Agents Plasma protein binding 010402 general chemistry Crystallography X-Ray Anticancer drugs 01 natural sciences General Biochemistry Genetics and Molecular Biology Biomaterials Structure-Activity Relationship Gold Compounds Biological property Gold compounds ESI-MS Protein metalation Tumor Cells Cultured Humans Cell Proliferation biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Cytochrome c Metals and Alloys HCT116 Cells 0104 chemical sciences biology.protein Drug Screening Assays Antitumor General Agricultural and Biological Sciences Organogold Compounds |
| Zdroj: | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 29(5) |
| ISSN: | 1572-8773 |
| Popis: | In the last few years gold(III) complexes have attracted growing attention in the medicinal chemistry community as candidate anticancer agents. In particular some organogold(III) compounds manifested quite attractive pharmacological behaviors in preclinical studies. Here we compare the chemical and biological properties of the novel organogold(III) complex [Au(bipy(dmb)-H)(NH(CO)CH3)][PF6] (Aubipy(aa)) with those of its parent compounds [Au(bipy(dmb)-H)(OH)][PF6] (Aubipy(c)) and [Au2(bipy(dmb)-H)2)(μ-O)][PF6]2 (Au2bipy(c)), previously synthesized and characterized. The three study compounds were comparatively assessed for their antiproliferative actions against HCT-116 cancer cells, revealing moderate cytotoxic effects. Proapoptotic and cell cycle effects were also monitored. Afterward, to gain additional mechanistic insight, the three gold compounds were challenged against the model proteins HEWL, RNase A and cytochrome c and reactions investigated through UV-Vis and ESI-MS analysis. A peculiar and roughly invariant protein metalation profile emerges in the three cases consisting of protein binding of {Au(bipy(dmb)-H)} moieties. The implications of these results are discussed in the frame of current knowledge on anticancer gold compounds. |
| Databáze: | OpenAIRE |
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