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dc.creatorKonstantinović, Jelena M.
dc.creatorKiris, Erkan
dc.creatorKota, Krishna P.
dc.creatorKugelman-Tonos, Johanny
dc.creatorVidenović, Milica
dc.creatorCazares, Lisa H.
dc.creatorTerzić-Jovanović, Nataša
dc.creatorVerbić, Tatjana
dc.creatorAnđelković, Boban D.
dc.creatorDuplantier, Allen J.
dc.creatorBavari, Sina
dc.creatorŠolaja, Bogdan
dc.date.accessioned2019-01-30T17:58:09Z
dc.date.available2019-01-30T17:58:09Z
dc.date.issued2018
dc.identifier.issn0022-2623
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2325
dc.description.abstractThe synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.en
dc.publisherAmer Chemical Soc, Washington
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationU.S. Defense Threat Reduction Agency/Joint Science and Technology Office
dc.relationSerbian Academy of Sciences and Arts
dc.relationNational Institute of Allergy and Infectious Diseases (U.S.) [5-U01AI082051-02, R33-AI101387]
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleNew Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Modelen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractКирис, Еркан; Виденовиц, Милица; Бавари, Сина; Кота, Крисхна П.; Константиновиц, Јелена; Дуплантиер, Aллен Ј.; Цазарес, Лиса Х.; Кугелман-Тонос, Јоханнy; Солаја, Богдан A.; Терзић Јовановић, Наташа; Вербиц, Татјана З.; Aнђелковић, Бобан Д.;
dc.citation.volume61
dc.citation.issue4
dc.citation.spage1595
dc.citation.epage1608
dc.citation.other61(4): 1595-1608
dc.citation.rankaM21
dc.description.otherThe peer-reviewed version: [http://cer.ihtm.bg.ac.rs/handle/123456789/2935]
dc.identifier.pmid29385334
dc.identifier.doi10.1021/acs.jmedchem.7b01710
dc.identifier.rcubConv_3884
dc.identifier.scopus2-s2.0-85042675131
dc.identifier.wos000426220900014
dc.type.versionpublishedVersion


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