Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities
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Date
Authors
Verlinden, Bianca K.
Niemand, Jandeli
Snyman, Janette
Sharma, Shirv K.
Beattie, Ross J.
Woster, Partick M.
Birkholtz, Lyn-Marie
Journal Title
Journal ISSN
Volume Title
Publisher
American Chemical Society
Abstract
A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized
and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium
falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3
μM, with the majority having effective IC50 values in the 100-650 nM range. Analogues arrested
parasitic growth within 24 hours of exposure due to a block in nuclear division and therefore asexual
development. Moreover, this effect appears to be cytotoxic and highly selective to malaria parasites
(>7000-fold lower IC50 against P. falciparum) and is not reversible by the exogenous addition of
polyamines. With this first report of potent antimalarial activity of polyamine analogues containing 3-7-
3 or 3-6-3 carbon backbones and substituted terminal urea- or thiourea moieties, we propose that these
compounds represent a structurally novel class of antimalarial agents.
Description
Keywords
Antimalarial drugs, (Bis)urea, (Bis)thiourea
Sustainable Development Goals
Citation
Verlinden, BK, Niemand, J, Snyman, J, Sharma, SK, Beattie, RJ, Woster, PM & Birkholtz, L-M 2011, 'Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities', Journal of Medicinal Chemistry, vol. 54, no. 19, pp. 6624-6633.