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Last Updated: 05/10/2023
Identification of new antimalarial compounds: a multidisciplinary strategy aiming the search for active classes against new molecular targets and different life stages of Plasmodium spp.
Objectives
*Original title in Portuguese: Identificação de novos compostos antimaláricos: uma estratégia multidisciplinar visando a busca por classes ativas contra novos alvos moleculares e diferentes estágios de vida do Plasmodium spp
The project intends to:
- Test the new classes of compounds against a panel of resistant strains.
- Test the speed of action of the new compounds in vitro.
- Elucidate the possible mechanism of action of the compounds from confocal microscopy and generation of P. falciparum strains resistant to the new compounds and subsequent analysis of the total genome.
- After identifying the potential molecular target, develop in silico models of protein-ligand structure through homology modeling and molecular docking.
- Implement in vitro gametocyte cultivation of P. falciparum for evaluating the activity of new classes of compounds.
- Confirm the activity of the most promising compounds against P. vivax in the artificial feeding model of Anopheles darlingi.
- Determine the inhibition potential of the candidates against isolates of P. vivax and P. falciparum circulating in the Brazilian Amazon, using samples of fresh and frozen isolates.
- Test the compounds against P. berghei in vivo.
Malaria, a disease caused by protozoa of the genus Plasmodium spp., is one of the major public health problems in the world. The disease occurs in 87 countries, with endemic in tropical and subtropical regions of Africa, Southeast Asia and Latin America. Half of the world’s population (3.3 billion people) is exposed to transmission of malaria in risk areas. In 2018, 228 million cases and 405,000 deaths were recorded according to the World Health Organization (WHO). The emergence of cases of resistance to available drugs makes the selection of new molecular targets in the parasite and the development of innovative chemotherapeutic agents extremely important. against the disease. In this context, the search for drugs that act against different stages of the life cycle of the parasite and that have an elucidated mechanism of action is fundamental importance. The proposed research project aims to broaden the approach multidisciplinary approach inherent to the drug planning process through the implementation of a new line of research at UNIFESP – Campus Baixada Santista, an emerging research center.
Feb 2021