Synthesis, Structural Characterization, Solution Behavior, and in Vitro Antiproliferative Properties of a Series of Gold Complexes with 2-(2鈥?Pyridyl)benzimidazole as Ligand: Comparisons of Gold(III)

详细信息    查看全文

• 作者：Maria Serratrice ; Maria A. Cinellu ; Laura Maiore ; Maria Pilo ; Antonio Zucca ; Chiara Gabbiani ; Annalisa Guerri ; Ida Landini ; Stefania Nobili ; Enrico Mini ; Luigi Messori
• 刊名：Inorganic Chemistry
• 出版年：2012
• 出版时间：March 5, 2012
• 年：2012
• 卷：51
• 期：5
• 页码：3161-3171
• 全文大小：455K
• 年卷期：v.51,no.5(March 5, 2012)
• ISSN：1520-510X

文摘

A variety of gold(III) and gold(I) derivatives of 2-(2鈥?pyridyl)benzimidazole (pbiH) were synthesized and fully characterized and their antiproliferative properties evaluated in a representative ovarian cancer cell line. The complexes include the mononuclear species [(pbi)AuX₂] (X = Cl, 1; OAc, 2), [(pbiH)AuCl] (3), [(pbiH)Au(PPh₃)][PF₆] (4-PF₆), and [(pbi)Au(L)] (L = PPh₃, 5; TPA, 6), and the binuclear gold(I)/gold(I) and gold(I)/gold(III) derivatives [(PPh₃)₂Au₂(渭₂-pbi)][PF₆] (10-PF₆), [ClAu(渭₃-pbi)AuCl₂] (7),and [(PPh₃)Au(渭₃-pbi)AuX₂][PF₆] (X = Cl, 8-PF₆; OAc, 9-PF₆). The molecular structures of 6, 7, and 10-PF₆ were determined by X-ray diffraction analysis. The chemical behavior of these compounds in solution was analyzed both by cyclic voltammetry in DMF and absorption UV鈥搗is spectroscopy in an aqueous buffer. Overall, the stability of these gold compounds was found to be acceptable for the cellular studies. For all complexes, relevant antiproliferative activities in vitro were documented against A2780 human ovarian carcinoma cells, either resistant or sensitive to cisplatin, with IC₅₀ values falling in the low micromolar or even in the nanomolar range. The investigated gold compounds were found to overcome resistance to cisplatin to a large degree. Results are interpreted and discussed in the frame of current knowledge on cytotoxic and antitumor gold compounds.