Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities

Loading...
Thumbnail Image

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.