Last Updated: 11/06/2024
Interaction of drugs as potential inhibitors of the isoprenoid pathway in Plasmodium falciparum and Plasmodium berghei
Objectives
*Original in Portuguese: Interação de fármacos como potenciais inibidores da via de isoprenóides em Plasmodium falciparum e Plasmodium berghei
This project will evaluate “in vivo” through the infection of Plasmodium berghei ANKA the combinations of drugs that have an effect additive or potentiating synergy on the 9 previously tested antimalarial drugs, which individually reduce the growth of Plasmodium falciparum “in vitro” through the inhibition of isoprenoid biosynthesis.
Malaria remains one of the main public health problems that affects about half of the world’s population. According to WHO, in 2016 there were 216 million cases of malaria and 445,000 deaths. This disease caused by parasites of the genus Plasmodium is difficult to eradicate, for this reason, it becomes necessary to look for new targets for the development of more effective chemotherapeutics to control the infection. isoprenoid pathway in P. falciparum, which are synthesized through the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway. This pathway being active in the intraerythrocytic stage of the parasite and not shared with the human host, becomes an interesting target for the development of new antimalarials. Isoprenoids are a diverse group of natural products with many functions and their synthesis is essential for survival of the parasite. In recent years, many drugs have been tested as blockers of isoprenoid synthesis in Plasmodium, and have allowed the identification of different targets of action of these drugs as potential antimalarials. Furthermore, as it has been already demonstrated, combinations of drugs that act on different targets of the isoprenoid pathway in the parasite have important supra-additivity effects.
Dec 2018 — Jan 2021
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