Activity and pharmacological profile of the DAQ-M metabolite in resistant malaria models.

• Grant number: 25/22345-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2025
• End date: October 31, 2027
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Anna Caroline Campos Aguiar
• Grantee: Ana Cristina Longuini
• 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 is a tropical disease highly prevalent in South America, Africa, and Southeast Asia, with more than 263 million cases and approximately 597,000 deaths reported in 2023 (WHO, 2024). It is caused by six Plasmodium species, with P. falciparum being the most severe and resistant to antimalarials, including artemisinin derivatives. Chloroquine (CQ), once widely used due to its low cost, was gradually replaced after resistance emerged, remaining recommended only in regions with sensitive strains. Currently, the WHO advises Artemisinin-based Combination Therapies (ACTs), although emerging resistance threatens global control efforts.Despite this, CQ continues to be used because of its affordability and accessibility. Since 1969, unsaturated CQ analogs such as DAQ have shown antimalarial activity with low toxicity. In 2018, our group demonstrated DAQ efficacy against resistant strains, and subsequent studies confirmed activity against P. falciparum and P. vivax, including clinical isolates in Brazil, as well as promising ADMET and pharmacokinetic profiles. DAQ's main metabolite, DAQM, also shows significant activity, but its role in resistance, particularly against artemisinin-resistant parasites, remains unclear.This project aims to further investigate DAQM, assessing its potential as a novel antimalarial candidate and evaluating its risk of inducing resistance.