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New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model
dc.creator | Konstantinović, Jelena M. | |
dc.creator | Kiris, Erkan | |
dc.creator | Kota, Krishna P. | |
dc.creator | Kugelman-Tonos, Johanny | |
dc.creator | Videnović, Milica | |
dc.creator | Cazares, Lisa H. | |
dc.creator | Terzić-Jovanović, Nataša | |
dc.creator | Verbić, Tatjana | |
dc.creator | Anđelković, Boban D. | |
dc.creator | Duplantier, Allen J. | |
dc.creator | Bavari, Sina | |
dc.creator | Šolaja, Bogdan | |
dc.date.accessioned | 2019-01-30T17:58:09Z | |
dc.date.available | 2019-01-30T17:58:09Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/2325 | |
dc.description.abstract | The 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.publisher | American Chemical Society (ACS) | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS// | |
dc.relation | U.S. Defense Threat Reduction Agency/Joint Science and Technology Office | |
dc.relation | Serbian Academy of Sciences and Arts | |
dc.relation | National Institute of Allergy and Infectious Diseases (U.S.) [5-U01AI082051-02, R33-AI101387] | |
dc.relation.isversionof | https://cer.ihtm.bg.ac.rs/handle/123456789/2935 | |
dc.relation.isreferencedby | https://cer.ihtm.bg.ac.rs/handle/123456789/4515 | |
dc.relation.isreferencedby | https://cer.ihtm.bg.ac.rs/handle/123456789/4516 | |
dc.relation.isreferencedby | https://cer.ihtm.bg.ac.rs/handle/123456789/4517 | |
dc.rights | restrictedAccess | |
dc.source | Journal of Medicinal Chemistry | |
dc.title | New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Кирис, 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.volume | 61 | |
dc.citation.issue | 4 | |
dc.citation.spage | 1595 | |
dc.citation.epage | 1608 | |
dc.citation.other | 61(4): 1595-1608 | |
dc.citation.rank | aM21 | |
dc.description.other | The peer-reviewed version: [http://cer.ihtm.bg.ac.rs/handle/123456789/2935] | |
dc.description.other | Supporting information I: [https://cer.ihtm.bg.ac.rs/handle/123456789/4515] | |
dc.description.other | Supporting information II: [https://cer.ihtm.bg.ac.rs/handle/123456789/4516] | |
dc.description.other | Supporting information III: [https://cer.ihtm.bg.ac.rs/handle/123456789/4517] | |
dc.identifier.pmid | 29385334 | |
dc.identifier.doi | 10.1021/acs.jmedchem.7b01710 | |
dc.identifier.scopus | 2-s2.0-85042675131 | |
dc.identifier.wos | 000426220900014 | |
dc.type.version | publishedVersion |