Cargando…

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

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, 5′-{[(Z)-4-amino-2-butenyl]m...

Descripción completa

Detalles Bibliográficos
Autores principales: le Roux, Dina, Burger, Pieter B., Niemand, Jandeli, Grobler, Anne, Urbán, Patricia, Fernàndez-Busquets, Xavier, Barker, Robert H., Serrano, Adelfa E., I. Louw, Abraham, Birkholtz, Lyn-Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940083/
https://www.ncbi.nlm.nih.gov/pubmed/24596666
http://dx.doi.org/10.1016/j.ijpddr.2013.11.003
Descripción
Sumario: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, 5′-{[(Z)-4-amino-2-butenyl]methylamino}-5′-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-5′-{[(Z)-4-aminobut-2-enyl]methylamino}-5′-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.