dc.creator | Opsenica, Igor | |
dc.creator | Terzić-Jovanović, Nataša | |
dc.creator | Opsenica, Dejan | |
dc.creator | Angelovski, Goran | |
dc.creator | Lehnig, Manfred | |
dc.creator | Eilbracht, Peter | |
dc.creator | Tinant, Bernard | |
dc.creator | Juranić, Zorica | |
dc.creator | Smith, Kirsten S. | |
dc.creator | Yang, Young S. | |
dc.creator | Diaz, Damaris S. | |
dc.creator | Smith, Philip L. | |
dc.creator | Milhous, Wilbur K. | |
dc.creator | Đoković, Dejan | |
dc.creator | Šolaja, Bogdan | |
dc.date.accessioned | 2019-09-20T12:46:30Z | |
dc.date.available | 2019-09-20T12:46:30Z | |
dc.date.issued | 2006 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/3096 | |
dc.description.abstract | Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed. | en |
dc.publisher | American Chemical Society (ACS) | |
dc.relation | info:eu-repo/grantAgreement/MESTD/MPN2006-2010/142022/RS// | |
dc.rights | restrictedAccess | |
dc.source | Journal of Medicinal Chemistry | |
dc.title | Tetraoxane antimalarials and their reaction with Fe(II) | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Доковиц, Дејан; Тинант, Бернард; Јураниц, Зорица; Милхоус, Wилбур К.; Шолаја, Богдан A.; Лехниг, Манфред; Еилбрацхт, Петер; Смитх, Кирстен С.; Yанг, Yоунг С.; Диаз, Дамарис С.; Опсеница, Дејан; Смитх, Пхилип Л.; Опсеница, Игор; Терзић-Јовановић, Наташа; Aнгеловски, Горан; | |
dc.citation.volume | 49 | |
dc.citation.issue | 13 | |
dc.citation.spage | 3790 | |
dc.citation.epage | 3799 | |
dc.citation.other | 49(13): 3790-3799 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 16789736 | |
dc.identifier.doi | 10.1021/jm050966r | |
dc.identifier.scopus | 2-s2.0-33745671105 | |
dc.identifier.wos | 000238446700008 | |
dc.type.version | publishedVersion | en |