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dc.creatorOpsenica, Igor
dc.creatorBurnett, James C.
dc.creatorGussio, Rick
dc.creatorOpsenica, Dejan M.
dc.creatorTodorović, Nina
dc.creatorLanteri, Charlotte A.
dc.creatorSciotti, Richard J.
dc.creatorGettayacamin, Montip
dc.creatorBasilico, Nicoletta
dc.creatorTaramelli, Donatella
dc.creatorNuss, Jonathan E.
dc.creatorWanner, Laura
dc.creatorPanchal, Rekha G.
dc.creatorŠolaja, Bogdan A.
dc.creatorBavari, Sina
dc.date.accessioned2018-11-22T00:18:09Z
dc.date.available2018-11-22T00:18:09Z
dc.date.issued2011
dc.identifier.issn0022-2623
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/1157
dc.description.abstractA 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.en
dc.publisherAmer Chemical Soc, Washington
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationNational Cancer Institute, National Institutes of Health [HHSN261200800001E]
dc.relationSerbian Academy of Sciences and Arts
dc.relationDefense Threat Reduction Agency [3.10084_09_RD_B, Y3CM 100505]
dc.relationNATOs Public Diplomacy Division [SfP983638]
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleA Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirusen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПанцхал, Рекха Г.; Лантери, Цхарлотте A.; Сциотти, Рицхард Ј.; Геттаyацамин, Монтип; Тарамелли, Донателла; Wаннер, Лаура; Басилицо, Ницолетта; Опсеница, Игор; Бавари, Сина; Нусс, Јонатхан Е.; Тодоровиц, Нина; Гуссио, Рицк; Бурнетт, Јамес Ц.; Шолаја, Богдан A.; Опсеница, Дејан;
dc.citation.volume54
dc.citation.issue5
dc.citation.spage1157
dc.citation.epage1169
dc.identifier.wos000287833300004
dc.identifier.doi10.1021/jm100938u
dc.citation.other54(5): 1157-1169
dc.citation.rankaM21
dc.identifier.pmid21265542
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-79952265619
dc.identifier.rcubKon_2157


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