Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites

dc.contributor.authorLe Roux, Dina
dc.contributor.authorBurger, Pieter Buys
dc.contributor.authorNiemand, Jandeli
dc.contributor.authorGrobler, Anne
dc.contributor.authorUrbán, Patricia
dc.contributor.authorFernàndez-Busquets, Xavier
dc.contributor.authorBarker, Robert H.
dc.contributor.authorSerrano, Adelfa
dc.contributor.authorLouw, Abraham Izak
dc.contributor.authorBirkholtz, Lyn-Marie
dc.contributor.emaillbirkholtz@up.ac.zaen_US
dc.date.accessioned2014-09-29T09:44:37Z
dc.date.available2014-09-29T09:44:37Z
dc.date.issued2014-04
dc.description.abstractS-adenosyl-L-methionine decarboxylase (AdoMetDC) in the polyamine biosynthesis pathway has been identified as a suitable drug target in Plasmodium falciparum parasites, which causes the most lethal form of malaria. Derivatives of an irreversible inhibitor of this enzyme, 50-{[(Z)-4-amino-2-butenyl]methylamino}- 50-deoxyadenosine (MDL73811), have been developed with improved pharmacokinetic profiles and activity against related parasites, Trypanosoma brucei. Here, these derivatives were assayed for inhibition of AdoMetDC from P. falciparum parasites and the methylated derivative, 8-methyl-50-{[(Z)- 4-aminobut-2-enyl]methylamino}-50-deoxyadenosine (Genz-644131) was shown to be the most active. The in vitro efficacy of Genz-644131 was markedly increased by nanoencapsulation in immunoliposomes, which specifically targeted intraerythrocytic P. falciparum parasites.en_US
dc.description.librarianhb2014en_US
dc.description.sponsorshipDepartment of Science and Technology through the South African Malaria Initiative, the University of Pretoria, the South African National Research Foundation and by grant BIO2011-25039 from the Ministerio de Economía y Competitividad, Spain, which included FEDER funds, and 2009SGR-760 from the Generalitat de Catalunya, Spainen_US
dc.description.urihttp://www.elsevier.com/locate/ijpddren_US
dc.identifier.citationLe Roux, D, Burger, PB, Niemand, J, Grobler, A, Urbán, P, Fernàndez-Busquets, X, Barker, RH, Serrano, AE, Louw, AI & Birkholtz, L.-M 2014,'Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites', International Journal for Parasitology : Drugs and Drug Resistance, vol. 4, no. 1, pp. 28-36.en_US
dc.identifier.issn2211-3207 (print)
dc.identifier.other10.1016/j.ijpddr.2013.11.003
dc.identifier.urihttp://hdl.handle.net/2263/42116
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rights© 2013 The Authors. Published by Elsevier Ltd. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License.en_US
dc.subjectPlasmodiumen_US
dc.subjectPolyaminesen_US
dc.subjectS-adenosyl-L-methionine decarboxylaseen_US
dc.subjectImmunoliposomesen_US
dc.titleNovel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasitesen_US
dc.typeArticleen_US

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