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Updated: Apr 2, 2026

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
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Disrupting Leishmania redox homeostasis: Mechanistic insights into a platinum-based antileishmanial complex

Marcus Sávio Araujo Garcia1, Vitor Klipel da Silva Bertolini1, Fernanda Ramos Gadelha1

  • 1Institute of Biology, University of Campinas, São Paulo, Brazil.

Journal of Inorganic Biochemistry
|March 31, 2026
PubMed

Insights

Platinum complexes show promise for treating leishmaniasis. The compound [PtCl(phpy)(PTA)] disrupts parasite mitochondria and redox balance, offering a new strategy against this neglected tropical disease.

Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Drug Discovery

Background:

  • Leishmaniasis is a neglected tropical disease requiring new treatments.
  • Platinum-based compounds are established anti-cancer drugs but underexplored for parasitic infections.

Purpose of the Study:

  • To investigate the antileishmanial activity and mechanism of a novel platinum(II) complex, [PtCl(phpy)(PTA)].
  • To explore platinum complexes as potential agents targeting redox and mitochondrial pathways in Leishmania.

Main Methods:

  • Synthesis and characterization of the platinum(II) complex [PtCl(phpy)(PTA)].
  • Evaluation of antileishmanial activity against Leishmania amazonensis promastigotes and axenic amastigotes.
  • Assessment of cytotoxicity against mammalian cells to determine selectivity index.
  • Biological and biochemical assays to elucidate the mechanism of action, including mitochondrial function and redox homeostasis analysis.

Main Results:

  • The platinum complex [PtCl(phpy)(PTA)] demonstrated low-micromolar antileishmanial activity with good selectivity.
  • The compound disrupted parasite mitochondrial bioenergetics, impairing respiration and membrane potential.
  • Inhibition of trypanothione reductase and induction of compensatory NADPH production via the pentose phosphate pathway were observed.

Conclusions:

  • Platinum(II) complexes can effectively target essential parasite pathways in Leishmania.
  • Metal-mediated redox disruption presents a viable strategy for developing novel antileishmanial drugs.
  • The compound [PtCl(phpy)(PTA)] warrants further investigation as a lead candidate for leishmaniasis treatment.
Keywords:
In vitroLeishmaniaMetal complexPlatinumRedox metabolismTrypanothione reductase

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