Related Experiment Video

Updated: Aug 13, 2026

Sexual Transmission of American Trypanosomes from Males and Females to Naive Mates
13:55

Sexual Transmission of American Trypanosomes from Males and Females to Naive Mates

Published on: January 27, 2019

Trypanosoma cruzi trypanothione reductase is inactivated by peroxidase-generated phenothiazine cationic radicals

J Gutierrez-Correa1, A H Fairlamb, A O Stoppani

  • 1Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Paraguay 2155, 1121-Buenos Aires, Argentina.

Free Radical Research
|May 1, 2001
PubMed

Insights

Phenothiazines (PTZ) combined with peroxidase and hydrogen peroxide irreversibly inhibit Trypanosoma cruzi trypanothione reductase (TR). Glutathione (GSH) protects TR, and PTZ radical cation formation is key for inactivation.

Area of Science:

  • Biochemistry
  • Parasitology
  • Drug Discovery

Background:

  • Trypanosoma cruzi trypanothione reductase (TR) is a crucial enzyme in the parasite's redox metabolism.
  • Inhibition of TR is a potential strategy for treating Chagas disease.
  • Phenothiazines (PTZ) are a class of compounds with diverse biological activities.

Purpose of the Study:

  • To investigate the irreversible inhibition of T. cruzi TR by peroxidase/H2O2/PTZ systems.
  • To elucidate the mechanism of TR inactivation and the role of PTZ radical cations.
  • To identify effective PTZ derivatives and peroxidases for TR inhibition.

Main Methods:

  • Enzyme activity assays to measure TR inhibition.
  • Kinetic analysis of TR inactivation.
  • Detection and characterization of PTZ radical cations.
  • Evaluation of different peroxidases and PTZ structures.

Main Results:

  • Peroxidase/H2O2/PTZ systems caused irreversible, biphasic inactivation of T. cruzi TR.
  • PTZ radical cation (PTZ+*) production was essential for TR inactivation.
  • Horseradish peroxidase, myeloperoxidase, and myoglobin effectively catalyzed PTZ+* formation.
  • Various phenothiazine derivatives showed varying efficacy in TR inhibition.
  • Glutathione (GSH) protected TR from inactivation by preventing PTZ+* activity.

Conclusions:

  • Peroxidase-catalyzed activation of phenothiazines generates reactive species that irreversibly inhibit T. cruzi TR.
  • The formation and reactivity of PTZ radical cations are critical for enzyme inactivation.
  • This study highlights a novel mechanism for targeting T. cruzi TR with potential therapeutic implications.

More Related Videos

Introducing a Gene Knockout Directly Into the Amastigote Stage of Trypanosoma cruzi Using the CRISPR/Cas9 System06:13

Introducing a Gene Knockout Directly Into the Amastigote Stage of Trypanosoma cruzi Using the CRISPR/Cas9 System

Published on: July 31, 2019

In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase08:48

In Vitro Drug Screening Against All Life Cycle Stages of Trypanosoma cruzi Using Parasites Expressing β-galactosidase

Published on: November 5, 2021

Related Concept Videos

Reactions at the Benzylic Position: Oxidation and Reduction00:59

Reactions at the Benzylic Position: Oxidation and Reduction

The benzylic position describes the position of a carbon atom attached directly to a benzene ring. Benzene by itself does not undergo oxidation. In contrast, the benzylic carbon is quite reactive in the presence of strong oxidizing agents such as KMnO4 or H2CrO4. Therefore, alkylbenzenes are readily oxidized to benzoic acid, irrespective of the type of alkyl groups.
Oxidation of Phenols to Quinones01:17

Oxidation of Phenols to Quinones

In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
Radical Autoxidation01:20

Radical Autoxidation

The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
American Trypanosomiasis01:22

American Trypanosomiasis

Chagas disease, or American trypanosomiasis, is a vector-borne parasitic infection caused by Trypanosoma cruzi, a flagellated protozoan (kinetoplastid) of the family Trypanosomatidae. The disease is endemic in Latin America, although cases are increasingly reported worldwide due to human migration. Transmission most commonly occurs when feces of infected triatomine bugs contaminate bite wounds or mucosal surfaces; additional routes include congenital, transfusional, transplant-related, and oral...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...