Phenotypic assays and quiescence studies for the identification of new piperaquine analogues.

• Grant number: 25/22386-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Anna Caroline Campos Aguiar
• Grantee: Kathleen Mangueira Lopes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/19708-0 - Identification of new antimalarial compounds: a multidisciplinary strategy aimed to search for potent chemical classes against new molecular targets and different stages of life of Plasmodium spp, AP.JP

Abstract

Malaria remains one of the most severe infectious diseases, with millions of cases and hundreds of thousands of deaths annually. Current treatment relies on Artemisinin-based Combination Therapies (ACTs), which have greatly reduced mortality since the 2000s. However, Plasmodium falciparum resistance to artemisinin, linked to the quiescence phenomenon, threatens ACT efficacy. In this state, ring-stage parasites enter dormancy under drug exposure, survive treatment, and resume growth once the drug is cleared, leading to recrudescence. Phenotypic assays such as RSA, PSA, recrudescence assays, and the more recent Quiescent-Stage Survival Assay (QSA) enable detection and characterization of this process.This project aims to evaluate piperaquine analogues previously identified by our group, using RSA, PSA, recrudescence assays, and QSA, along with morphological analysis by transmission electron microscopy. We expect these compounds to show activity against quiescent parasites, significantly delaying or preventing recrudescence. Implementing QSA and complementary approaches will support the development of novel antimalarial candidates capable of overcoming artemisinin resistance.