Related Experiment Video
Updated: Jan 16, 2026
Author Spotlight: Understanding the Propagation of Closed Circular Extrachromosomal rDNA Containing Element (CERE) in Naegleria gruberi
Published on: June 21, 2024
Mentha rotundifolia, a Source of Amoebicidal Agents Against Naegleria fowleri
Meriam Ben Youssef1,2,3, Javier Chao-Pellicer1,4,5, Eduardo Hernández-Álvarez3
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, 38296 La Laguna, Santa Cruz de Tenerife, Spain.
Abstract:
Current therapies for Primary Amoebic Meningoencephalitis (PAM) present several limitations; consequently, there is an urgent need to develop new therapeutic agents. In this regard, we undertook bioassay-guided isolation of Mentha rotundifolia leaves which allowed the identification of ursolic acid (1) as the main bioactive metabolite against two ATCC strains of Naegleria fowleri (ATCC® 30808TM and ATCC® 30215TM). Moreover, ten ursolic acid derivatives (2-11) were synthesized through esterification and nucleophilic substitution to obtain halo or amino ester derivatives. Among these derivatives, compound 7 exhibited the highest activity against the N. fowleri ATCC® 30808TM strain with an IC50 value of 28.66 µM, whereas compound 10 showed the top activity against the N. fowleri ATCC® 30215TM strain with an IC50 of 7.61 µM, surpassing the efficacy of the reference drug, miltefosine. Both compounds, 7 and 10, showed a good selectivity index and hence low toxicity in vitro. Structure-activity relationship studies revealed that the type of acylating agent played a crucial role in the activity. Furthermore, both compounds induced autophagy and apoptosis-like processes in both treated N. fowleri strains. These results highlight the potential of ursolic acid-related triterpenoids as drug scaffolds and identify M. rotundifolia as a promising natural source of amoebicidal agents against PAM.
Insights
New research identifies ursolic acid from Mentha rotundifolia as a potential treatment for Primary Amoebic Meningoencephalitis (PAM). Derivatives showed potent amoebicidal activity, offering hope for novel therapeutic agents against Naegleria fowleri infections.
Area of Science:
- Natural Product Chemistry
- Medicinal Chemistry
- Parasitology
Background:
- Current therapies for Primary Amoebic Meningoencephalitis (PAM) are limited, necessitating the development of new treatments.
- Naegleria fowleri is the causative agent of PAM, a rare but highly fatal infection.
Purpose of the Study:
- To isolate and identify bioactive compounds from Mentha rotundifolia with activity against Naegleria fowleri.
- To synthesize and evaluate ursolic acid derivatives for enhanced amoebicidal efficacy and reduced toxicity.
Main Methods:
- Bioassay-guided isolation of Mentha rotundifolia leaves to identify ursolic acid.
- Chemical synthesis of ten ursolic acid derivatives via esterification and nucleophilic substitution.
- In vitro evaluation of compounds against Naegleria fowleri strains (ATCC® 30808™ and ATCC® 30215™), including IC50 determination and selectivity index calculation.
- Assessment of compound-induced cellular mechanisms, including autophagy and apoptosis.
Main Results:
- Ursolic acid was identified as the main bioactive metabolite from Mentha rotundifolia against Naegleria fowleri.
- Synthesized derivatives showed significant amoebicidal activity; compounds 7 and 10 exhibited superior efficacy compared to miltefosine against specific strains.
- Compounds 7 and 10 demonstrated good selectivity indices, indicating low in vitro toxicity.
- Structure-activity relationship studies indicated the importance of the acylating agent in determining activity.
- Both active compounds induced autophagy and apoptosis-like processes in Naegleria fowleri.
Conclusions:
- Mentha rotundifolia is a promising source of natural amoebicidal agents.
- Ursolic acid derivatives represent a potential new class of therapeutic scaffolds for treating Primary Amoebic Meningoencephalitis.
- Further investigation into these triterpenoids could lead to the development of effective drugs against Naegleria fowleri infections.
Related Concept Videos
01:27Diversity of Protists IV
01:26Physical Properties of Amines