Activity evaluation of new 4-quinolone compounds against sexual forms of Plasmodium spp.

• Grant number: 22/05873-1
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2022
• Effective date (End): August 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Anna Caroline Campos Aguiar
• Grantee: Yasmin Annunciato
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , 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
• Associated scholarship(s): 23/02543-3 - Evaluation of the activity of new 4-quinolones compounds against hepatic and sexual forms of Plasmodium spp., BE.EP.MS

Abstract

Malaria has a prominent position among tropical diseases, generating a serious global impact due to its burden of mortality and morbidity, with consequences for the socioeconomic development of communities and the health and productivity of populations living in endemic regions of the disease. Currently, cases of resistance to treatment in combination with artemisinin derivatives (ACTs) have already been reported in 5 countries in the Southeast Asian region, and the emergence of multidrug-resistant strains is a worrying scenario, in which the search for new candidates for antimalarials of Innovative action is essential to achieve the objectives of controlling and eliminating the disease. Furthermore, the development of effective therapies to block transmission in order to achieve the goal of malaria eradication is of great importance. In this sense, the class of 4-quinolone compounds (Synthesized by Prof. Dr. Arlene Correa from the Federal University of São Carlos- UFSCar) was recently evaluated and had its activity against asexual forms of P. falciparum (3d7-sensitive) previously determined. and characterized (IC50< 1 µM). Furthermore, the action of this class of compounds was characterized by our group (Oliveira, 2021 https://doi.org/10.1016/j.ejmcr.2021.100012), targeting the BC1 complex of P. falciparum, which is an important target for the search for transmission blockers. In this sense, it is of great importance to evaluate the effect of this new class of compounds against the sexual stage of P. falciparum (strain NF54). The development of this project will allow the identification of the most active candidates that will be later evaluated in the model of artificial feeding of Anopheles darlingi in the blood of a patient infected with P. vivax (NF54). This second stage of the project will be carried out in collaboration with Dr. Maisa Araújo (FIOCRUZ-RO).