Trypanocidal activity of melamine-based nitroheterocycles

Stewart, M.L., Bueno, G.J., Baliani, A., Klenke, B., Brun, R., Brock, J.M., Gilbert, I.,H. and Barrett, M.,P., (2004) Trypanocidal activity of melamine-based nitroheterocycles. Antimicrobial Agents and Chemotherapy, 48(5), pp. 1733-1738. (doi:10.1128/AAC.48.5.1733-1738.2004)

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A series of nitroheterocyclic compounds were designed with linkages to melamine or benzamidine groups that are known substrates of the P2 aminopurine and other transporters in African trypanosomes of the brucei group. Several compounds showed in vitro trypanotoxicity with 50% inhibitory concentrations in the submicromolar range. Although most compounds interacted with the P2 transporter, as judged by their ability to inhibit adenosine transport via this carrier, uptake through this route was not necessary for activity since TbAT1-null mutant parasites, deficient in this transporter, retained sensitivity to these drugs. One compound, a melamine-linked nitrofuran, also showed pronounced activity against parasites in mice. Studies into the mode of action of this compound indicated that neither reductive, nor oxidative, stress were related to its trypanocidal activity ruling out a genotoxic effect in T. brucei, distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Barrett, Professor Michael
Authors: Stewart, M.L., Bueno, G.J., Baliani, A., Klenke, B., Brun, R., Brock, J.M., Gilbert, I.,H., and Barrett, M.,P.,
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Antimicrobial Agents and Chemotherapy
Journal Abbr.:Antimicrob. Agents Chemother.
Publisher:American Society for Microbiology
ISSN (Online):1098-6596

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