Verlinden, Bianca K.Niemand, JandeliSnyman, JanetteSharma, Shirv K.Beattie, Ross J.Woster, Partick M.Birkholtz, Lyn-Marie2012-02-072012-10-312011-10Verlinden, 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. 6624-6633.0022-2623 (print)1520-4804 (online)10.1021/jm200463zhttp://hdl.handle.net/2263/18027A 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.en© 2011 Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see, http://pubs.acs.org/journal/jmcmar. This article is embargoed by the publisher until October 2012.Antimalarial drugs(Bis)urea(Bis)thioureaMalaria -- ChemotherapyAntimalarialsPlasmodium -- ControlPolyaminesAlkylating agentsPostprint Article