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dc.contributor.authorTillotson, Joseph
dc.contributor.authorKedzior, Magdalena
dc.contributor.authorGuimarães, Larissa
dc.contributor.authorRoss, Alison B.
dc.contributor.authorPeters, Tara L.
dc.contributor.authorAmbrose, Andrew J.
dc.contributor.authorSchmidlin, Cody J.
dc.contributor.authorZhang, Donna D.
dc.contributor.authorCosta-Lotufo, Letícia V.
dc.contributor.authorRodríguez, Abimael D.
dc.contributor.authorSchatz, Jonathan H.
dc.contributor.authorChapman, Eli
dc.date.accessioned2019-04-30T17:29:21Z
dc.date.available2019-04-30T17:29:21Z
dc.date.issued2017-09-01
dc.identifier.citationTillotson, J., Kedzior, M., Guimarães, L., Ross, A. B., Peters, T. L., Ambrose, A. J., ... & Schatz, J. H. (2017). ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A. Bioorganic & medicinal chemistry letters, 27(17), 4082-4085.en_US
dc.identifier.issn0960894X
dc.identifier.doi10.1016/j.bmcl.2017.07.045
dc.identifier.urihttp://hdl.handle.net/10150/632157
dc.description.abstractActivation of translation initiation is a common trait of cancer cells. Formation of the heterotrimeric eukaryotic initiation factor F (eIF4F) complex is the rate-limiting step in 5' m7GpppN cap-dependent translation. This trimeric complex includes the eIF4E cap binding protein, the eIF4G scaffolding protein, and the DEAD box RNA helicase eIF4A. eIF4A is an ATP-dependent helicase and because it is the only enzyme in the eIF4F complex, it has been shown to be a potential therapeutic target for a variety of malignancies. To this end, we have used a simple ATPase biochemical screen to survey several hundred marine and terrestrial derived natural products. Herein, we report the discovery of two natural products from marine sources, elisabatin A (1) and allolaurinterol (2), which show low mu M inhibition of eIF4A ATPase activity. Enzymological analyses revealed 1 and 2 to be ATP-competitive, and cellular evaluations showed reasonable cytotoxicity against A549 (lung cancer) and MDA-MA-468 (breast cancer) cell lines. However, only compound 2 showed potent inhibition of helicase activity congruent with its ATPase inhibitory activity. (C) 2017 Elsevier Ltd. All rights reserved.en_US
dc.description.sponsorshipUniversity of Arizona; National Institutes of Health (NIH) Training Grant [T32 GM008804, T32 HL007249]; National Institute of Environmental Health Sciences Training Grant [T32 ES007091]en_US
dc.language.isoenen_US
dc.publisherPERGAMON-ELSEVIER SCIENCE LTDen_US
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0960894X17307412en_US
dc.rights© 2017 Elsevier Ltd. All rights reserveden_US
dc.subjectCanceren_US
dc.subjectTranslationen_US
dc.subjecteIF4Aen_US
dc.subjectNatural productsen_US
dc.subjectDEAD box helicaseen_US
dc.subjectInhibitoren_US
dc.titleATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4Aen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Pharm, Dept Pharmacol & Toxicolen_US
dc.identifier.journalBIOORGANIC & MEDICINAL CHEMISTRY LETTERSen_US
dc.description.note24 month embargo; available online 19 July 2017.en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleBioorganic & Medicinal Chemistry Letters
dc.source.volume27
dc.source.issue17
dc.source.beginpage4082
dc.source.endpage4085


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