Development of dihydrofolate reductase inhibitors from the genus plasmodium applying CADD methods

According to the World Health Organization, approximately half of the world’s population was at risk of malaria in the year 2019, being more susceptible to infection: children, pregnant women, HIV patients, in addition to populations living in areas with a high transmission rate. In that same year, 229 million cases of malaria were reported, with a death toll of approximately 409,000, which shows the complexity and dimension of this global public health issue (WHO, 2019). Malaria is caused by parasites of the genus Plasmodium, with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, the etiologic agents responsible for most human infections. These different species vary geographically: P. falciparum is found prevalently in the sub-Saharan region and Haiti, accounting for 90-100% of infections in these regions, while P. vivax is predominant in South America, Central America and the Indian subcontinent. Malaria transmission occurs mainly through the bite of the female Anopheles mosquito, and it can also be transmitted through the placenta, blood transfusion, or even by sharing disposable needles from a person positive for malaria. The disease cycle begins during the hematophagy process in which the vector transmits the parasite to the host’s blood circulation. After entering the body, the protozoan infects the liver cells, undergoing asexual reproduction and, after a maturation period of 6 to 14 days, the infected liver cells are ruptured, releasing the merozoite forms into the bloodstream. The merozoites, in turn, invade the erythrocytes and continue to reproduce until the red blood cell also ruptures, releasing more parasites systemically and initiating another cycle of asexual development and multiplication. Parasites found in the host’s blood can be ingested by the mosquito during hematophagous feeding, and spread within the host population occurs. Sexual reproduction of Plasmodium also occurs in the mosquito, in which the parasite migrates to the salivary glands, making the mosquito its vector.

Project details

Drug-based Strategies
Product Development

Apr 2022

Brazil