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dc.creatorBurnett, J.C.
dc.creatorOpsenica, Dejan
dc.creatorSriraghavan, K.
dc.creatorPanchal, R.G.
dc.creatorRuthel, G.
dc.creatorHermone, A.R.
dc.creatorNguyen, T.L.
dc.creatorKenny, T.A.
dc.creatorLane, D.J.
dc.creatorMcGrath, C.F.
dc.creatorSchmidt, J.J.
dc.creatorVennerstrom, J.L.
dc.creatorGussio, R.
dc.creatorŠolaja, Bogdan
dc.creatorBavari, S.
dc.date.accessioned2019-01-30T17:16:34Z
dc.date.available2019-01-30T17:16:34Z
dc.date.issued2007
dc.identifier.issn0022-2623
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/361
dc.description.abstractWe previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC50's ranged from 3.2 to 17 μM). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.en
dc.publisherAmerican Chemical Society (ACS)
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142022/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleA refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloproteaseen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractКеннy, Т.A.; Гуссио, Р.; Веннерстром, Ј.Л.; Сцхмидт, Ј.Ј.; МцГратх, Ц.Ф.; Лане, Д.Ј.; Бавари, С.; Нгуyен, Т.Л.; Хермоне, A.Р.; Рутхел, Г.; Панцхал, Р.Г.; Срирагхаван, К.; Опсеница, Дејан; Шолаја, Б.A.; Бурнетт, Ј.Ц.;
dc.citation.volume50
dc.citation.issue9
dc.citation.spage2127
dc.citation.epage2136
dc.citation.other50(9): 2127-2136
dc.citation.rankaM21
dc.identifier.pmid17417831
dc.identifier.doi10.1021/jm061446e
dc.identifier.rcubConv_4068
dc.identifier.scopus2-s2.0-34247633446
dc.identifier.wos000245954600015
dc.type.versionpublishedVersion


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