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Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases

Alba Martínez-Flórez1, Melina Galizzi2, Luis Izquierdo3

  • 1Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.

International Journal for Parasitology. Drugs and Drug Resistance
|August 24, 2020
PubMed

Insights

Repurposing anti-cancer drugs like dichloroacetic acid (DCA) and metformin (MET) shows promise against parasitic diseases. These compounds, targeting cancer cell metabolism, demonstrated antiparasitic activity in vitro against Leishmania, Trypanosoma, and Plasmodium species.

Area of Science:

  • Parasitology
  • Drug Discovery
  • Cancer Biology

Background:

  • Malaria, leishmaniasis, and trypanosomiasis are significant global health issues, particularly in developing nations.
  • These parasitic diseases share high glucose consumption with cancer cells, suggesting a common metabolic vulnerability.
  • Limited access to diagnostics and treatments exacerbates the impact of these neglected tropical diseases.

Purpose of the Study:

  • To investigate the antiparasitic potential of six anti-cancer drugs by repurposing them for treating leishmaniasis, trypanosomiasis, and malaria.
  • To evaluate the efficacy of dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR) against various parasitic species in vitro.
  • To explore the hypothesis that drugs targeting cancer cell metabolism can be effective against parasitic infections.

Main Methods:

  • In vitro testing of six selected anti-cancer compounds against Leishmania infantum, Trypanosoma brucei, Trypanosoma cruzi, and Plasmodium falciparum.
  • Assessment of parasite viability and burden following treatment with DCA, 3BP, 2DG, LND, MET, and SIR.
  • Comparative analysis of drug efficacy across different parasitic models.

Main Results:

  • Dichloroacetic acid (DCA) and 3-bromopyruvic acid (3BP) reduced intra-macrophagic Leishmania infantum amastigotes.
  • Metformin (MET) and other tested compounds (except 2DG) decreased Trypanosoma brucei survival.
  • DCA, 2DG, lonidamine (LND), and MET exhibited activity against Trypanosoma cruzi.
  • DCA, 2DG, LND, MET, and sirolimus (SIR) demonstrated anti-plasmodial activity against Plasmodium falciparum.

Conclusions:

  • Repurposing anti-cancer drugs that interfere with cellular metabolism offers a promising strategy for developing new antiparasitic therapies.
  • The tested compounds, particularly DCA and MET, show potential for treating multiple parasitic diseases.
  • Further research into these drug candidates could lead to novel treatment options for neglected tropical diseases.
Keywords:
2-deoxy-D-glucose3-bromopyruvateBionergetic modulatorsDichloroacetateLonidamineMetforminProtozoan parasitesRepurposingSirolimus

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