000161661 001__ 161661
000161661 005__ 20190522142434.0
000161661 0247_ $$2doi$$a10.1007/s00775-010-0654-x
000161661 022__ $$a0949-8257
000161661 02470 $$2ISI$$a000280239100009
000161661 037__ $$aARTICLE
000161661 245__ $$aMetabolization of [Ru(η6-C6H5CF3)(pta)Cl2]: a cytotoxic RAPTA-type complex with a strongly electron withdrawing arene ligand
000161661 269__ $$a2010
000161661 260__ $$bSpringer-Verlag$$c2010
000161661 336__ $$aJournal Articles
000161661 500__ $$aNational Licences
000161661 520__ $$aThe anticancer ruthenium-arene compd. [Ru(η6-C6H5CF3)(pta)Cl2] (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane), termed RAPTA-CF3, with the electron-withdrawing α,α,α-trifluorotoluene ligand, is one of the most cytotoxic RAPTA compds. known. To rationalize the high obsd. cytotoxicity, the hydrolysis of RAPTA-CF3 in water and brine (100 mM sodium chloride) and its reactions with the protein ubiquitin and a double-stranded oligonucleotide (5'-GTATTGGCACGTA-3') were studied using NMR spectroscopy, high-resoln. Fourier transform ion cyclotron resonance mass spectrometry, and gel electrophoresis. The aquation of the ruthenium-chlorido complex was accompanied by a loss of the arene ligand, independent of the chloride concn., which is a special property of the compd. not obsd. for other ruthenium-arene complexes with relatively stable ruthenium-arene bonds. Accordingly, the mass spectra of the biomol. reaction mixts. contained mostly [Ru(pta)]-biomol. adducts, whereas [Ru(pta)(arene)] adducts typical of other RAPTA compds. were not obsd. in the protein or DNA binding studies. Gel electrophoresis expts. revealed a significant degree of decompn. of the oligonucleotide, which was more pronounced in the case of RAPTA-CF3 compared with RAPTA-C. Consequently, facile arene loss appears to be responsible for the increased cytotoxicity of RAPTA-CF3. Graphical abstr.: RAPTA-CF3 is a fast-acting cytotoxic compd. that degrades DNA and has a mode of action fundamentally different from that of other ruthenium(II)-arene compds.
000161661 6531_ $$aAnticancer drugs
000161661 6531_ $$aBioorganometallic chemistry
000161661 6531_ $$aDNA interactions
000161661 6531_ $$aMass spectrometry
000161661 6531_ $$aProtein binding
000161661 6531_ $$aPlasma-Mass Spectrometry
000161661 6531_ $$aHuman Serum-Albumin
000161661 6531_ $$aCapillary-Electrophoresis
000161661 6531_ $$aIn-Vitro
000161661 6531_ $$aAnticancer Activity
000161661 6531_ $$aPreclinical Development
000161661 6531_ $$aMetallodrug Research
000161661 6531_ $$aBinding Sites
000161661 6531_ $$aPhase-I
000161661 6531_ $$aCompound
000161661 700__ $$aEgger, Alexander E.
000161661 700__ $$aHartinger, Christian G.
000161661 700__ $$0240150$$g173186$$aRenfrew, Anna K.
000161661 700__ $$aDyson, Paul J.$$g149418$$0240015
000161661 773__ $$j15$$tJBIC, Journal of Biological Inorganic Chemistry$$k6$$q919-927
000161661 8564_ $$uhttps://infoscience.epfl.ch/record/161661/files/775_2010_Article_654.pdf$$zPUBLISHER'S VERSION$$s617108
000161661 909C0 $$xU9$$0252010$$pLCOM
000161661 909CO $$pSB$$particle$$ooai:infoscience.tind.io:161661
000161661 917Z8 $$x179141
000161661 937__ $$aEPFL-ARTICLE-161661
000161661 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000161661 980__ $$aARTICLE