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dc.creatorOpsenica, Igor
dc.creatorTerzić-Jovanović, Nataša
dc.creatorOpsenica, Dejan
dc.creatorAngelovski, Goran
dc.creatorLehnig, Manfred
dc.creatorEilbracht, Peter
dc.creatorTinant, Bernard
dc.creatorJuranić, Zorica
dc.creatorSmith, Kirsten S.
dc.creatorYang, Young S.
dc.creatorDiaz, Damaris S.
dc.creatorSmith, Philip L.
dc.creatorMilhous, Wilbur K.
dc.creatorĐoković, Dejan
dc.creatorŠolaja, Bogdan
dc.date.accessioned2019-09-20T12:46:30Z
dc.date.available2019-09-20T12:46:30Z
dc.date.issued2006
dc.identifier.issn0022-2623
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/3096
dc.description.abstractMixed 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.publisherAmerican Chemical Society (ACS)
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142022/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleTetraoxane antimalarials and their reaction with Fe(II)en
dc.typearticle
dc.rights.licenseARR
dcterms.abstractДоковиц, 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.volume49
dc.citation.issue13
dc.citation.spage3790
dc.citation.epage3799
dc.citation.other49(13): 3790-3799
dc.citation.rankM21
dc.identifier.pmid16789736
dc.identifier.doi10.1021/jm050966r
dc.identifier.scopus2-s2.0-33745671105
dc.identifier.wos000238446700008
dc.type.versionpublishedVersionen


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