Screening and Identification of Pathogen Box® Compounds with anti-Trypanosoma evansi Activity

Abstract

The development of new drugs targeting neglected animal diseases is imperative. In Asia and South America, Trypanosoma evansi is a pathogen that affects horses and other species, causing economic losses associated with reduced animal productivity and death. In order to accelerate the identification of drugs with activity against neglected diseases, Medicines for Malaria Venture has developed Pathogen Box®, a library of 400 different molecules. The present work aimed to identify compounds present in the Pathogen Box® library, measuring in vitro activity against T. evansi. Among the 400 compounds, 5 showed anti-T.evansi activity: pentamidine, MMV688410, MMV687273, MMV022478 and auranofin. Suramin, a trypanocidal activity molecule present on the Pathogen Box® reference compound list, demonstrated no anti-T. evansi activity in the in vitro assays. MMV688410 is the most promising candidate because it induces death and reduces the number of parasites in cell culture, and mainly because its mechanism of action is probably associated with inhibition of trypanosomal reductase enzyme, an exclusive target of trypanosomatides. Further in vitro and in vivo assays are needed to determine the efficacy of the compounds identified in this work, especially by associating tissue distribution and the ability of drugs to cross the blood brain barrier, as T. evansi is able to invade the central nervous system.