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

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dc.contributor.author Le Roux, Dina
dc.contributor.author Burger, Pieter Buys
dc.contributor.author Niemand, Jandeli
dc.contributor.author Grobler, Anne
dc.contributor.author Urbán, Patricia
dc.contributor.author Fernàndez-Busquets, Xavier
dc.contributor.author Barker, Robert H.
dc.contributor.author Serrano, Adelfa
dc.contributor.author Louw, Abraham Izak
dc.contributor.author Birkholtz, Lyn-Marie
dc.date.accessioned 2014-09-29T09:44:37Z
dc.date.available 2014-09-29T09:44:37Z
dc.date.issued 2014-04
dc.description.abstract S-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.librarian hb2014 en_US
dc.description.sponsorship Department 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, Spain en_US
dc.description.uri http://www.elsevier.com/locate/ijpddr en_US
dc.identifier.citation Le 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.issn 2211-3207 (print)
dc.identifier.other 10.1016/j.ijpddr.2013.11.003
dc.identifier.uri http://hdl.handle.net/2263/42116
dc.language.iso en en_US
dc.publisher Elsevier en_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.subject Plasmodium en_US
dc.subject Polyamines en_US
dc.subject S-adenosyl-L-methionine decarboxylase en_US
dc.subject Immunoliposomes en_US
dc.title Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites en_US
dc.type Article en_US


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