Synthesis, characterization and anticancer activity in vitro evaluation of novel dicyanoaurate (I)-based complexes

• Published in: Life sciences (1973) 2020-06, Vol.251, p.117635-13, Article 117635
• Main Authors: Karadağ, Ahmet, Aydın, Ali, Tekin, Şaban, Akbaş, Hüseyin, Şahin, Onur, Sen, Fatih
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antiproliferative effect; Antitumor activity; Cadmium; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemotherapy; Chlorocebus aethiops; Coordination compounds; Copper; Crystal structure; Cyanates - administration & dosage; Cyanates - chemical synthesis; Cyanates - pharmacology; Cyanides; Cytoskeleton; Cytotoxicity; Diamines; Dicyanoaurate (I); DNA topoisomerase; Dosage; Dose-Response Relationship, Drug; Gold; Gold - administration & dosage; Gold - pharmacology; Humans; Inhibitory Concentration 50; Measurement methods; Medical treatment; Molecular structure; Neoplasms - drug therapy; Neoplasms - pathology; Nickel; Nucleic acids; Pharmacology; Proteins; Solubility; Spectroscopic titration; Synthesis; Toxicity; Tumor cell lines; Vero Cells
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117635

Molecular structures containing gold, such as auranofin, have been extensively studied in the diagnosis and treatment of many diseases, including cancer treatment. The pharmacological properties of the newly synthesized unique gold-ligand structures have been reported for different cancer cell lines. However, findings on bishydeten-metal salt complexes with gold are rare. In this work, the synthesis of five novel cyanide-bridged coordination compounds having the closed formulae [Ni(bishydeten)][Au(CN)2]2 (1), [Cu(bishydeten)][Au(CN)2]2 (2), [Zn(bishydeten)2Au3(CN)4][Au2(CN)3] (3), [Cd(bishydeten)0,5]2[Au(CN)2]4.2H2O (4), and [Cd(bishydeten)2][Au(CN)2]2 (5) (where bisyhdeten = N,N-bis(2-hydroxyethyl)ethylene diamine), and their characterization by elemental, infrared, ESI-MS, X-ray (for 2) and thermic measurement methods were performed. Complexes 1 and 3 are thermally more stable than the other three complexes. For these, pharmacological adequacies were also tested. The nucleic acid and protein binding affinities of the Au (I) compounds were also estimated by spectroscopic and electrophoretic techniques. Au (I) complexes were identified as strong chemotherapeutic with mild cytotoxicity, and they demonstrated a dose-dependent inhibition on the growth of cancer cells with IC50 at 0.11 to 0.47 μM. Investigation of mechanisms of action on cells revealed that Au (I) compounds managed to inhibit cell migration and led to a decrease in cytoskeletal proteins such as CK7 and CK20. However, Au (I) compounds failed to inhibit DNA topoisomerase I. Overall, and we suggest that potent antiproliferative activity, mild cytotoxicity, good solubility, and micromolar dosage of Au (I) compounds containing bisyhdeten-metal derivatives render them the potential focus of further studies as chemotherapeutic agents. •Synthesis of five novel cyanide bridged coordination compounds•One of the highest effectiveness of AuNPs for the inhibition of proliferation of Vero HeLa HT29, and C6 cancer lines•Its proliferative effect by reducing DNA synthesis and apoptosis-inducing cell cycle stages.