Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim

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dc.citation.firstpage4311en_US
dc.citation.journalTitleMarine Drugsen_US
dc.citation.lastpage4325en_US
dc.citation.volumeNumber12en_US
dc.contributor.authorCheng , Chunweien_US
dc.contributor.authorLiu, Yanen_US
dc.contributor.authorBalasis, Maria E.en_US
dc.contributor.authorGarner, Thomas P.en_US
dc.contributor.authorLi, Jerryen_US
dc.contributor.authorSimmons, Nicholas L.en_US
dc.contributor.authorBerndt, Norberten_US
dc.contributor.authorSong, Haoen_US
dc.contributor.authorPan, Lilien_US
dc.contributor.authorQin, Yongen_US
dc.contributor.authorNicolaou, K.C.en_US
dc.contributor.authorGavathiotis, Evripidisen_US
dc.contributor.authorSebti , Said M.en_US
dc.contributor.authorLi, Rongshien_US
dc.contributor.orgBioScience Research Collaborativeen_US
dc.date.accessioned2014-08-29T20:22:43Zen_US
dc.date.available2014-08-29T20:22:43Zen_US
dc.date.issued2014en_US
dc.description.abstractA series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.en_US
dc.identifier.citationCheng , Chunwei, Liu, Yan, Balasis, Maria E., et al.. "Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim." <i>Marine Drugs,</i> 12, (2014) MDPI: 4311-4325. http://dx.doi.org/10.3390/md12084311.en_US
dc.identifier.doihttp://dx.doi.org/10.3390/md12084311en_US
dc.identifier.urihttps://hdl.handle.net/1911/77133en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordmarinopyrrolesen_US
dc.subject.keywordprotein-protein interaction disruptorsen_US
dc.subject.keywordapoptosisen_US
dc.subject.keywordSARen_US
dc.titleMarinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bimen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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