In vivo investigations of selected diamidine compounds against Trypanosoma evansi using a mouse model.
Surra is an animal pathogenic protozoan infection, caused by Trypanosoma evansi, that develops into a fatal wasting disease. Control measures rely on diagnosis and treatment. However, with the continuous emergence of drug resistance, this tactic is failing, and the pressing need for new chemotherapeutic agents is becoming critical. With the introduction of novel aromatic diamidines, a new category of antitrypanosomal drugs was discovered. Nevertheless, their efficacy within a T. evansi-infected mouse model was not known. In total, 30 compounds previously selected based on their in vitro activity were tested in a T. evansi mouse model of infection. Six of the compounds were capable of curing T. evansi-infected mice at drug doses as low as 0.5 and 0.25 mg/kg of body weight administered for 4 consecutive days, and they were more effective than the standard drugs suramin, diminazene, and quinapyramine. After all selection criteria were applied, three diamidine compounds (DB 75, DB 867, and DB 1192) qualified as lead compounds and were considered to have the potential to act as preclinical candidates against T. evansi infection.
Gillingwater
Kirsten
K
Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland.
Kumar
Arvind
A
Anbazhagan
Mariappan
M
Boykin
David W
DW
Tidwell
Richard R
RR
Brun
Reto
R
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010419:Pentamidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D014345:Trypanosoma / Q000187:drug effects* / Q000472:pathogenicity*; D014352:Trypanosomiasis / Q000188:drug therapy* / Q000469:parasitology*
D014344:Trypanocidal Agents; D010419:Pentamidine