Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity.

ABSTRACT: Trematode infections such as schistosomiasis and fascioliasis cause significant morbidity in an estimated 250 million people worldwide and the associated agricultural losses are estimated at more than US$ 6 billion per year. Current chemotherapy is limited. Triosephosphate isomerase (TIM), an enzyme of the glycolytic pathway, has emerged as a useful drug target in many parasites, including Fasciola hepatica TIM (FhTIM). We identified 21 novel compounds that selectively inhibit this enzyme. Using microscale thermophoresis we explored the interaction between target and compounds and identified a potent interaction between the sulfonyl-1,2,4-thiadiazole (compound 187) and FhTIM, which showed an IC₅₀ of 5 µM and a K_d of 66 nM. In only 4 hours, this compound killed the juv

SUBMITTER: Ferraro F 

PROVIDER: S-EPMC7018972 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature