000841291 001__ 841291
000841291 005__ 20240625095118.0
000841291 0247_ $$2doi$$a10.1016/j.bmcl.2017.09.011
000841291 0247_ $$2ISSN$$a0960-894X
000841291 0247_ $$2ISSN$$a1464-3405
000841291 0247_ $$2pmid$$apmid:28919339
000841291 0247_ $$2WOS$$aWOS:000412863700018
000841291 0247_ $$2altmetric$$aaltmetric:26311269
000841291 037__ $$aFZJ-2017-08382
000841291 082__ $$a540
000841291 1001_ $$00000-0002-8253-3382$$aMinniti, Elirosa$$b0
000841291 245__ $$aNovel xanthone-polyamine conjugates as catalytic inhibitors of human topoisomerase IIα
000841291 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2017
000841291 3367_ $$2DRIVER$$aarticle
000841291 3367_ $$2DataCite$$aOutput Types/Journal article
000841291 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1513232100_28643
000841291 3367_ $$2BibTeX$$aARTICLE
000841291 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000841291 3367_ $$00$$2EndNote$$aJournal Article
000841291 520__ $$aIt has been proposed that xanthone derivatives with anticancer potential act as topoisomerase II inhibitors because they interfere with the ability of the enzyme to bind its ATP cofactor. In order to further characterize xanthone mechanism and generate compounds with potential as anticancer drugs, we synthesized a series of derivatives in which position 3 was substituted with different polyamine chains. As determined by DNA relaxation and decatenation assays, the resulting compounds are potent topoisomerase IIα inhibitors. Although xanthone derivatives inhibit topoisomerase IIα-catalyzed ATP hydrolysis, mechanistic studies indicate that they do not act at the ATPase site. Rather, they appear to function by blocking the ability of DNA to stimulate ATP hydrolysis. On the basis of activity, competition, and modeling studies, we propose that xanthones interact with the DNA cleavage/ligation active site of topoisomerase IIα and inhibit the catalytic activity of the enzyme by interfering with the DNA strand passage step.
000841291 536__ $$0G:(DE-HGF)POF3-574$$a574 - Theory, modelling and simulation (POF3-574)$$cPOF3-574$$fPOF III$$x0
000841291 588__ $$aDataset connected to CrossRef
000841291 7001_ $$0P:(DE-HGF)0$$aByl, Jo Ann W.$$b1
000841291 7001_ $$0P:(DE-HGF)0$$aRiccardi, Laura$$b2
000841291 7001_ $$0P:(DE-HGF)0$$aSissi, Claudia$$b3
000841291 7001_ $$0P:(DE-HGF)0$$aRosini, Michela$$b4
000841291 7001_ $$00000-0003-4022-5661$$aDe Vivo, Marco$$b5
000841291 7001_ $$0P:(DE-HGF)0$$aMinarini, Anna$$b6$$eCorresponding author
000841291 7001_ $$00000-0002-2550-4884$$aOsheroff, Neil$$b7$$eCorresponding author
000841291 773__ $$0PERI:(DE-600)1501505-1$$a10.1016/j.bmcl.2017.09.011$$gVol. 27, no. 20, p. 4687 - 4693$$n20$$p4687 - 4693$$tBioorganic & medicinal chemistry letters$$v27$$x0960-894X$$y2017
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.pdf$$yRestricted
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.gif?subformat=icon$$xicon$$yRestricted
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.jpg?subformat=icon-180$$xicon-180$$yRestricted
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.jpg?subformat=icon-640$$xicon-640$$yRestricted
000841291 8564_ $$uhttps://juser.fz-juelich.de/record/841291/files/1-s2.0-S0960894X17308934-main.pdf?subformat=pdfa$$xpdfa$$yRestricted
000841291 909CO $$ooai:juser.fz-juelich.de:841291$$pVDB
000841291 9101_ $$0I:(DE-588b)5008462-8$$60000-0003-4022-5661$$aForschungszentrum Jülich$$b5$$kFZJ
000841291 9131_ $$0G:(DE-HGF)POF3-574$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$vTheory, modelling and simulation$$x0
000841291 9141_ $$y2017
000841291 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000841291 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000841291 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000841291 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000841291 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOORG MED CHEM LETT : 2015
000841291 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000841291 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000841291 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000841291 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000841291 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000841291 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000841291 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000841291 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000841291 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000841291 920__ $$lyes
000841291 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0
000841291 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x1
000841291 980__ $$ajournal
000841291 980__ $$aVDB
000841291 980__ $$aI:(DE-Juel1)IAS-5-20120330
000841291 980__ $$aI:(DE-Juel1)INM-9-20140121
000841291 980__ $$aUNRESTRICTED