Related Experiment Video
Updated: Oct 8, 2025
Development of Leishmania Species Strains with Constitutive Expression of eGFP
Published on: April 21, 2023
Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
Atteneri López-Arencibia1,2,3,4, Ines Sifaoui1,3,4, María Reyes-Batlle1,2,3,4
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Campus de Anchieta, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Spain.
Abstract:
The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. amazonensis promastigotes and intracellular amastigotes. Moreover, studies on the mechanism of cell death showed that compounds 3 and 5 induced an apoptotic process while the compounds 7, 9 and 10 seem to induce an autophagic mechanism. The present findings underline the potential of these five molecules as novel therapeutic leishmanicidal agents.
Insights
Researchers screened antileishmanial compounds against Leishmania amazonensis, identifying five potent drug candidates. These compounds show promise as novel leishmanicidal agents, with distinct mechanisms of action including apoptosis and autophagy.
Area of Science:
- Parasitology
- Drug Discovery
- Medicinal Chemistry
Background:
- Leishmaniasis affects over 1 million people annually, caused by the protozoan parasite *Leishmania*.
- Current treatments for leishmaniasis are associated with toxicity, high cost, administration challenges, and emerging drug resistance.
- There is a critical need for novel, effective, and safer therapeutic agents against leishmaniasis.
Purpose of the Study:
- To screen antileishmanial activity of Pathogen Box compounds against *Leishmania amazonensis*.
- To compare the structures and cytotoxicity of identified active compounds.
- To investigate the mechanisms of cell death induced by promising leishmanicidal compounds.
Main Methods:
- Screening of Medicine for Malaria Venture's Pathogen Box compounds for antileishmanial activity.
- Dose-dependent inhibition assays against *L. amazonensis* promastigotes and intracellular amastigotes.
- Cytotoxicity assessments and studies on the mechanism of cell death (apoptosis and autophagy).
Main Results:
- Five compounds (MMV676388, MMV690103, MMV022029, MMV022478, and MMV021013) demonstrated significant dose-dependent inhibition of *L. amazonensis* proliferation.
- Compounds MMV676388 and MMV690103 induced an apoptotic cell death pathway.
- Compounds MMV022029, MMV022478, and MMV021013 appeared to induce an autophagic mechanism of cell death.
Conclusions:
- The identified five compounds exhibit significant leishmanicidal potential against *Leishmania amazonensis*.
- The compounds display distinct mechanisms of action, involving either apoptosis or autophagy, offering diverse therapeutic strategies.
- These molecules represent promising leads for the development of novel leishmanicidal drugs to combat leishmaniasis.
More Related Videos
12:22A Parasite Rescue and Transformation Assay for Antileishmanial Screening Against Intracellular Leishmania donovani Amastigotes in THP1 Human Acute Monocytic Leukemia Cell Line
Published on: December 30, 2012
08:17Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
