A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A

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dc.contributor.authorHarrell, William A. Jr.
dc.contributor.authorVieira, Rebecca C.
dc.contributor.authorEnsel, Susan M.
dc.contributor.authorMontgomery, Vicki
dc.contributor.authorGuernieri, Rebecca
dc.contributor.authorEccard, Vanessa S.
dc.contributor.authorCampbell, Yvette
dc.contributor.authorRoxas-Duncan, Virginia
dc.contributor.authorCardellina, John H. II
dc.contributor.authorWebb, Robert P.
dc.contributor.authorSmith, Leonard A.
dc.contributor.departmentChemistryen_US
dc.date.accessioned2020-02-24T15:19:06Z
dc.date.available2020-02-24T15:19:06Z
dc.date.issued2017-02-01
dc.description.abstractOur initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay.en_US
dc.description.urihttps://ezproxy.stevenson.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&db=mnh&AN=28043798&site=eds-live&scope=siteen_US
dc.format.extent4 pagesen_US
dc.genreJournal Articleen_US
dc.identifierdoi:10.13016/m2ajjf-hilt
dc.identifier.citationHarrell, W. A., Jr, Vieira, R. C., Ensel, S. M., Montgomery, V., Guernieri, R., Eccard, V. S., Campbell, Y., Roxas-Duncan, V., Cardellina, J. H., 2nd, Webb, R. P., & Smith, L. A. (2017). A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A. Bioorganic & Medicinal Chemistry Letters, 27(3), 675–678. https://doi.org/10.1016/j.bmcl.2016.11.019en_US
dc.identifier.issn1464-3405
dc.identifier.uri10.1016/j.bmcl.2016.11.019
dc.identifier.urihttp://hdl.handle.net/11603/17360
dc.language.isoenen_US
dc.publisherBioorganic & Medicinal Chemistry Lettersen_US
dc.subjectBotulinum Toxins, Type A--antagonists & inhibitorsen_US
dc.subjectHydroxyquinolines--chemistryen_US
dc.subjectAnimalsen_US
dc.subjectBinding Sitesen_US
dc.subjectBotulinum Toxins, Type A--metabolismen_US
dc.subjectHydroxyquinolines--metabolismen_US
dc.subjectHydroxyquinolines--toxicityen_US
dc.subjectInhibitory Concentration 50en_US
dc.subjectMiceen_US
dc.subjectPhrenic Nerve/metabolismen_US
dc.subjectPhrenic Nerve--drug effectsen_US
dc.subjectPhrenic Nerve--metabolismen_US
dc.subjectProtein Bindingen_US
dc.subjectSerogroupen_US
dc.subjectStructure-Activity Relationshipen_US
dc.titleA matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype Aen_US
dc.typeTexten_US

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