In vitro activity and preliminary toxicity of various diamidine compounds against Trypanosoma evansi

Trypanosome evansi is an animal pathogenic protozoan, causing a wasting disease called Surra, which is broadly distributed in a wide range of mammalian hosts. Chemotherapy is the most efficient control method, which depends on four drugs. Unfortunately, with the appearance of resistance to these drugs, their effective use is threatened, emphasising a need to find new drugs. Diamidines bind to the minor groove of DNA at AT-rich sites and exert their anti-trypanosomal activity by inhibiting one or more DNA dependent enzymes or by directly impeding the transcription process. In total, 67 novel diamidine compounds were tested in vitro to determine activity against an animal pathogenic Chinese kinetoplastic T. evansi strain. In comparison, a human pathogenic Trypanosome brucei rhodesiense strain and a P2 transporter knock out of a Trypanosome brucei brucei strain were also tested. All diamidine compounds tested in this study against T. evansi produced inhibitory concentration (IC50) values below 50 nM. The results demonstrate that these compounds are highly active against T. evansi in vitro. In addition, preliminary in vivo toxicity tests were performed on all 67 diamidines with 69% of the compounds showing no acute toxicity at an intra-peritoneal dose of 100 mg/kg. (C) 2010 Elsevier B.V. All rights reserved.