Synthesis, Characterization, and in Vitro Evaluation of Novel Ruthenium(II) 6-Arene Imidazole Complexes

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• 作者：Carsten A. Vock ; Claudine Scolaro ; Andrew D. Phillips ; Rosario Scopelliti ; Gianni Sava ; Paul J. Dyson
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：September 7, 2006
• 年：2006
• 卷：49
• 期：18
• 页码：5552 - 5561
• 全文大小：186K
• 年卷期：v.49,no.18(September 7, 2006)
• ISSN：1520-4804

文摘

Ten complexes of general formula [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-arene)Cl₂(L)], [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-arene)Cl(L)₂][X], and [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-arene)(L)₃][X]₂ (mages/gifchars/eta.gif" BORDER=0 >⁶-arene = benzene, p-cymene; L = imidazole, benzimidazole, N-methylimidazole, N-butylimidazole,N-vinylimidazole, N-benzoylimidazole; X = Cl, BF₄, BPh₄) have been prepared and characterized byspectroscopy. The structures of five representative compounds have been established in the solid state bysingle-crystal X-ray diffraction. All the new compounds were assessed by the same in vitro screening assaysapplied to [imidazole-H][trans-RuCl₄(DMSO)(imidazole)] (NAMI-A) and [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-arene)Cl₂(1,3,5-triaza-7-phosphaadamantane)] (RAPTA) compounds. It was found that the new compounds show essentially thesame order of cytotoxicity as the RAPTA compounds toward cancer cells. Several of the compounds wereselective toward cancer cells in that they were less (or not) cytotoxic toward nontumorigenic cells that areused to model healthy human cells. Thus, two of the compounds, [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-p-cymene)Cl(vinylimid)₂][Cl](vinylimid = N-vinylimidazole) and [Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-benzene)(mimid)₃][BF₄]₂ (mimid = N-methylimidazole), havebeen selected for a more detailed in vivo evaluation.