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dc.contributor.authorWright, Colin W.*
dc.contributor.authorAddae-Kyereme, Jonathan A.*
dc.contributor.authorBreen, Anthony G.*
dc.contributor.authorBrown, John E.*
dc.contributor.authorCox, Marlene F.*
dc.contributor.authorCroft, S.L.*
dc.contributor.authorGokcek, Yaman*
dc.contributor.authorKendrick, H.*
dc.contributor.authorPhillips, Roger M.*
dc.contributor.authorPollet, Pamela L.*
dc.date.accessioned2009-11-17T12:08:00Z
dc.date.available2009-11-17T12:08:00Z
dc.date.issued2001
dc.identifier.citationWright, C.W., Addae-Kyereme, J., Breen, A.G., Brown, J.E. and Cox, M.F. et al. (2001). Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. Journal of Medicinal Chemistry. Vol. 44, No. 19, pp. 3187-3194.en
dc.identifier.urihttp://hdl.handle.net/10454/3946
dc.descriptionNoen
dc.description.abstractThe indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of ß-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg-1 day-1 ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (¿Tm value) or toxicity in the mouse¿malaria model.en
dc.language.isoenen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1021/jm010929+en
dc.subjectInfectionen
dc.subjectProtozoal diseaseen
dc.subjectMalariaen
dc.subjectDNAen
dc.subjectCryptolepine analoguesen
dc.subjectAntimalarial agents.en
dc.titleSynthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


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