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dc.creatorTerzić-Jovanović, Nataša
dc.creatorKonstantinović, Jelena M.
dc.creatorTot, Miklos
dc.creatorBurojevic, Jovana
dc.creatorDjurkovic-Djakovic, Olgica
dc.creatorSrbljanović, Jelena
dc.creatorŠtajner, Tijana
dc.creatorVerbić, Tatjana
dc.creatorZlatović, Mario
dc.creatorMachado, Marta
dc.creatorAlbuquerque, Ines S
dc.creatorPrudencio, Miguel
dc.creatorSciotii, Richard J
dc.creatorPecic, Stevan
dc.creatorDAlessandro, Sarah
dc.creatorTaramelli, Donatella
dc.creatorŠolaja, Bogdan
dc.date.accessioned2019-01-30T17:50:25Z
dc.date.available2019-01-30T17:50:25Z
dc.date.issued2016
dc.identifier.issn0022-2623
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1953
dc.description.abstractThe syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 mu M and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 mu M). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 +/- 0.37 mu M). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.en
dc.publisherAmerican Chemical Society (ACS)
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41019/RS//
dc.relationBill & Melinda Gates Foundation [OPP1040394]
dc.relationSerbian Academy of Sciences and Arts
dc.relationFundacao para a Ciencia e Tecnologia, Portugal [PTDC/SAUMIC/117060/2010]
dc.rightsrestrictedAccess
dc.sourceJournal of Medicinal Chemistry
dc.titleReinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?en
dc.typearticle
dc.rights.licenseARR
dcterms.abstractДјурковиц-Дјаковиц, Олгица; Константиновиц, Јелена; Солаја, Богдан A; Стајнер, Тијана; Пециц, Стеван; Тарамелли, Донателла; Терзић Јовановић, Наташа; Вербиц, Татјана; Златовиц, Марио; Aлбуqуерqуе, Инес С; Тот, Миклос; Буројевиц, Јована; Србљановиц, Јелена; Мацхадо, Марта; Пруденцио, Мигуел; Сциотии, Рицхард Ј; ДAлессандро, Сарах;
dc.citation.volume59
dc.citation.issue1
dc.citation.spage264
dc.citation.epage281
dc.citation.other59(1): 264-281
dc.citation.rankaM21
dc.identifier.pmid26640981
dc.identifier.doi10.1021/acs.jmedchem.5b01374
dc.identifier.rcubConv_3480
dc.identifier.scopus2-s2.0-84955243433
dc.identifier.wos000368564400019
dc.type.versionpublishedVersion


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