Development of new anti-trypanosomasis drug by in silico screening, in vitro assay and X-ray analysis

Abstract

Chagas’ disease, African trypanosomiasis, and leishmaniasis are some examples of neglected tropical diseases (NTDs) caused by the parasite Trypanosoma. While nifurtimox and benznidazole are currently available for treatment of Chagas' disease, they have major drawbacks, such as side effects and their insufficient effectiveness in the chronic stage. To develop a novel anti-trypanosomiasis drug, we performed virtual screening for 4.8 million small molecules of spermidine synthase as the target protein and conducted an in vitro enzyme assay to determine IC50 value. As a result, we identified hit compounds that inhibit T. cruzi SRM (TcSRM). We also determined the TcSRM-ligand complex structure using X-ray crystallography.