Abstract
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 iron-chelating agents may serve as lead compounds for novel anti-trypanosomal drug development.
Highlights
Trypanosoma brucei and T. congolense are the causative agents of sleeping sickness in humans and nagana in cattle, respectively
The anti-trypanosomal activities of these compounds are approaching those of commercial drugs used to treat sleeping sickness and nagana (diminazene aceturate (Berenil®): IC50 = 0.5 μM) previously determined for bloodstream forms of T. brucei 427-221a and T. congolense STIB910 under identical experimental conditions [11]
Iron deprivation may be a new strategy for the treatment of African trypanosomiasis
Summary
Trypanosoma brucei and T. congolense are the causative agents of sleeping sickness in humans and nagana in cattle, respectively. Over 60 million people living in 36 sub-Saharan countries are threatened with sleeping sickness [1] and 48000 deaths were reported in 2002 [2]. 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]. Drug resistance in African trypanosomes is increasing [6,7]. New strategies to treat African trypanosomes are required
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
