Determination of the Phenotypic Profile of a Triazolopyrimidine Derivative.

• Grant number: 25/11777-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Anna Caroline Campos Aguiar
• Grantee: Vinícius Borges Hashitani
• 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, a disease caused by protozoa of the genus Plasmodium spp., remains one of the major public health problems worldwide. Plasmodium falciparum is the predominant parasite in sub-Saharan Africa, where it is associated with high mortality rates. The emergence and spread of multidrug-resistant P. falciparum strains highlight the urgent need to discover new compounds active against this parasite. In this context, the triazolopyrimidine class has been evaluated by our research group, and a compound with potent activity against both drug-sensitive (IC¿¿ = 86 nM) and drug-resistant (IC¿¿ = 100 nM) P. falciparum isolates has been identified. These data were previously published in the European Journal of Medicinal Chemistry (209, 2021, 112941). As part of the ongoing development of this compound series, it is now necessary to deepen in vitro studies using a representative compound, aiming at its phenotypic characterization. To this end, we will evaluate the speed of action of the triazolopyrimidine compound. Parasites will be incubated with the compound for different time periods - 24, 48, and 72 hours - and we will subsequently monitor the IC¿¿ values obtained at each time point to understand the compound's rate of action in inhibiting parasite growth.¹ Another assay to be conducted will assess the stage-specific activity. For this, parasites will be synchronized at the ring (0-3 h), trophozoite (16-24 h), and schizont (24-36 h) stages, in order to determine whether the compound preferentially acts at a specific stage of the parasite's life cycle.² Finally, we will evaluate the activity profile of the compound against a panel of strains resistant to currently available antimalarials (Dd2 - chloroquine and pyrimethamine, K1 - chloroquine and pyrimethamine, TM90 - atovaquone, IPC - artemisinin derivatives). (AU)