Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites
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Date
Authors
Le Roux, Dina
Burger, Pieter Buys
Niemand, Jandeli
Grobler, Anne
Urbán, Patricia
Fernàndez-Busquets, Xavier
Barker, Robert H.
Serrano, Adelfa
Louw, Abraham Izak
Birkholtz, Lyn-Marie
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
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.
Description
Keywords
Plasmodium, Polyamines, S-adenosyl-L-methionine decarboxylase, Immunoliposomes
Sustainable Development Goals
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.