Development of Organometallic Ruthenium-Arene Anticancer Drugs That Resist Hydrolysis

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• 作者：Wee Han Ang ; Elisa Daldini ; Claudine Scolaro ; Rosario Scopelliti ; Lucienne Juillerat-Jeannerat ; Paul J. Dyson
• 刊名：Inorganic Chemistry
• 出版年：2006
• 出版时间：October 30, 2006
• 年：2006
• 卷：45
• 期：22
• 页码：9006 - 9013
• 全文大小：241K
• 年卷期：v.45,no.22(October 30, 2006)
• ISSN：1520-510X

文摘

With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands havebeen prepared and studied. The new complexes, Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-cymene)(PTA)(C₂O₄) (1) and Ru(mages/gifchars/eta.gif" BORDER=0 >⁶-cymene)(PTA)(C₆H₆O₄)(2), were found to be highly soluble and kinetically more stable than their RAPTA precursor that contains twochloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibitedsignificantly lower pK_a values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growthproliferation (as determined by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidencedby matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hencerealizing a strategy for developing a new generation of stable and highly water-soluble RAPTA adducts.