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Updated: Jan 9, 2026

Measurement of Heme Synthesis Levels in Mammalian Cells
09:43

Measurement of Heme Synthesis Levels in Mammalian Cells

Published on: July 9, 2015

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The heme A synthase Cox15, as a target of redox-active 3-benzylmenadiones with antiparasitic activity

Marcelo L Merli1, Claudia Serot2, Cindy Vallières3

  • 1Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Universidad Nacional de Rosario (UNR), Rosario, Santa Fe, Argentina.

Antimicrobial Agents and Chemotherapy
|December 10, 2025
PubMed

Insights

Cruzidione, a novel anti-parasitic drug, targets heme A synthase Cox15 in Trypanosoma cruzi. This inhibition disrupts parasite respiration, offering a new therapeutic strategy for Chagas disease.

Area of Science:

  • Biochemistry
  • Parasitology
  • Drug Discovery

Background:

  • Chagas disease, caused by Trypanosoma cruzi, is a neglected parasitic infection with limited treatment options.
  • The development of new anti-T. cruzi drugs is crucial due to the scarcity of effective therapies.
  • A library of 3-benzylmenadione derivatives was synthesized, with cruzidione showing high efficacy against T. cruzi.

Purpose of the Study:

  • To elucidate the mode of action of cruzidione against Trypanosoma cruzi.
  • To identify the primary molecular target of cruzidione.
  • To explore the potential of Cox15 as a novel antiparasitic drug target.

Main Methods:

  • Utilized Saccharomyces cerevisiae as a model organism to study cruzidione's mechanism.
  • Investigated the effect of specific Cox15 mutations on yeast sensitivity to cruzidione.
  • Assessed the impact of cruzidione on cytochrome c oxidase activity and heme content in T. cruzi.
  • Examined the role of NADH-dehydrogenase in cruzidione bioactivation using the yeast model.

Main Results:

  • A mutation in yeast Cox15 (S429F) conferred high sensitivity to cruzidione.
  • Cruzidione treatment led to the loss of cytochrome c oxidase activity.
  • Cruzidione significantly reduced heme content and oxygen consumption in T. cruzi.
  • NADH-dehydrogenase was identified as a key enzyme in cruzidione bioactivation, producing metabolites that inhibit Cox15.

Conclusions:

  • Heme A synthase Cox15 is the primary target of cruzidione.
  • Cruzidione inhibits T. cruzi growth by disrupting heme biosynthesis and respiration.
  • Cox15 represents a promising novel target for the development of new antiparasitic drugs.

Keywords:
antiparasitic drugdrug mode of actionmitochondrial respiratory chainyeast model

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