dc.creator | Opsenica, Igor | |
dc.creator | Burnett, James C. | |
dc.creator | Gussio, Rick | |
dc.creator | Opsenica, Dejan | |
dc.creator | Todorović, Nina | |
dc.creator | Lanteri, Charlotte A. | |
dc.creator | Sciotti, Richard J. | |
dc.creator | Gettayacamin, Montip | |
dc.creator | Basilico, Nicoletta | |
dc.creator | Taramelli, Donatella | |
dc.creator | Nuss, Jonathan E. | |
dc.creator | Wanner, Laura | |
dc.creator | Panchal, Rekha G. | |
dc.creator | Šolaja, Bogdan | |
dc.creator | Bavari, Sina | |
dc.date.accessioned | 2019-01-30T17:28:14Z | |
dc.date.available | 2019-01-30T17:28:14Z | |
dc.date.issued | 2011 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/901 | |
dc.description.abstract | A 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.publisher | American Chemical Society (ACS) | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS// | |
dc.relation | National Cancer Institute, National Institutes of Health [HHSN261200800001E] | |
dc.relation | Serbian Academy of Sciences and Arts | |
dc.relation | Defense Threat Reduction Agency [3.10084_09_RD_B, Y3CM 100505] | |
dc.relation | NATOs Public Diplomacy Division [SfP983638] | |
dc.rights | openAccess | |
dc.source | Journal of Medicinal Chemistry | |
dc.title | A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Панцхал, Рекха Г.; Бавари, Сина; Сциотти, Рицхард Ј.; Лантери, Цхарлотте A.; Гуссио, Рицк; Нусс, Јонатхан Е.; Бурнетт, Јамес Ц.; Басилицо, Ницолетта; Тодоровић, Нина; Опсеница, Дејан; Опсеница, Игор; Солаја, Богдан A.; Тарамелли, Донателла; Wаннер, Лаура; Геттаyацамин, Монтип; | |
dc.citation.volume | 54 | |
dc.citation.issue | 5 | |
dc.citation.spage | 1157 | |
dc.citation.epage | 1169 | |
dc.citation.other | 54(5): 1157-1169 | |
dc.citation.rank | aM21 | |
dc.identifier.pmid | 21265542 | |
dc.identifier.doi | 10.1021/jm100938u | |
dc.identifier.fulltext | https://cer.ihtm.bg.ac.rs//bitstream/id/9486/899.pdf | |
dc.identifier.scopus | 2-s2.0-79952265619 | |
dc.identifier.wos | 000287833300004 | |
dc.type.version | publishedVersion | |