Ethyl Pyruvate Emerges as a Safe and Fast Acting Agent against Trypanosoma brucei by Targeting Pyruvate Kinase Activity

PloS One
Netsanet WorkuGerd Birkenmeier

Abstract

Human African Trypanosomiasis (HAT) also called sleeping sickness is an infectious disease in humans caused by an extracellular protozoan parasite. The disease, if left untreated, results in 100% mortality. Currently available drugs are full of severe drawbacks and fail to escape the fast development of trypanosoma resistance. Due to similarities in cell metabolism between cancerous tumors and trypanosoma cells, some of the current registered drugs against HAT have also been tested in cancer chemotherapy. Here we demonstrate for the first time that the simple ester, ethyl pyruvate, comprises such properties. The current study covers the efficacy and corresponding target evaluation of ethyl pyruvate on T. brucei cell lines using a combination of biochemical techniques including cell proliferation assays, enzyme kinetics, phasecontrast microscopic video imaging and ex vivo toxicity tests. We have shown that ethyl pyruvate effectively kills trypanosomes most probably by net ATP depletion through inhibition of pyruvate kinase (Ki = 3.0±0.29 mM). The potential of ethyl pyruvate as a trypanocidal compound is also strengthened by its fast acting property, killing cells within three hours post exposure. This has been demonstrated using...Continue Reading

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Citations

Mar 2, 2016·Drug Development and Industrial Pharmacy·Eva SnejdrovaJana Nguyenova
Sep 21, 2017·MBio·Conrad L EptingDavid M Engman
Sep 1, 2016·PloS One·Gerd BirkenmeierFaramarz Dehghani
Jun 4, 2021·Biochemistry·JianChao YuAlexander Shekhtman

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Methods Mentioned

BETA
ELISA

Software Mentioned

SIGMAPLOT
GraphPad Prism
SoftMax Pro
Freemake Video Converter . exe
GraphPad

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