Kinetoplastid Biology and Disease

African trypanosomes exert significant morbidity and mortality in man and livestock. Only a few drugs are available for the treatment of trypanosome infections and therefore, the development of new anti-trypanosomal agents is required. Previously it has been shown that bloodstream-form trypanosomes are sensitive to the iron chelator deferoxamine. In this study the effect of 13 iron chelators on the growth of Trypanosoma brucei, T. congolense and human HL-60 cells was tested in vitro. With the exception of 2 compounds, all chelators exhibited anti-trypanosomal activities, with 50% inhibitory concentration (IC50) values ranging between 2.1 – 220 μM. However, the iron chelators also displayed cytotoxicity towards human HL-60 cells and therefore, only less favourable selectivity indices compared to commercially available drugs. Interfering with iron metabolism may be a new strategy in the treatment of trypanosome infections. More specifically, lipophilic ironchelating agents may serve as lead compounds for novel anti-trypanosomal drug development. Background Trypanosoma brucei and T. congolense are the causative agents of sleeping sickness in humans and nagana in cattle, respectively. The protozoan parasites live extracellularly in blood and tissue fluids of mammals and are transmitted by the bite of infected tsetse flies (Glossina spp.). Over 60 million people living in 36 sub-Saharan countries are threatened with sleeping sickness [1] and 48000 deaths were reported in 2002 [2]. In addition, 46 million cattle are exposed to the risk of contracting nagana and the disease costs an estimated 1340 million USD per year [3]. Chemotherapy of African trypanosomiasis still relies on drugs developed decades ago and some of these display serious toxic side effects [4,5]. In addition, drug resistance in African trypanosomes is increasing [6,7]. Thus, new strategies to treat African trypanosomes are required. In contrast to mammalian cells, bloodstream-form trypanosomes require only small amounts of iron for growth [8]. The reason for this is that bloodstream-form trypanosomes lack cytochromes and contain only four iron-dependent enzymes: aconitase, alternative oxidase, ribonucleotide reductase and superoxide dismutase. Recently, it has been shown that incubation of T. brucei bloodstream forms with the iron chelator deferoxamine results in growth inhibition of the parasite [9]. The compound does not inhibit iron-containing enzymes directly but acts by chelating cellular iron thus preventing its incorporation into newly synthesised apoproteins [9]. Here we investigated the trypanocidal activity of 13 chelators known to be able to complex iron ions against bloodstream forms of T. brucei and T. congolense in vitro. For Published: 16 August 2006 Kinetoplastid Biology and Disease 2006, 5:3 doi:10.1186/1475-9292-5-3 Received: 30 March 2006 Accepted: 16 August 2006 This article is available from: http://www.kinetoplastids.com/content/5/1/3 © 2006 Merschjohann and Steverding; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.