Novos derivados da primaquina planejados com possíveis antiplasmódicos

Abstract

Malaria is an infectious disease of parasitic origin caused by protozoa of the Plasmodium genus, which are transmitted through the bite of infected female mosquitoes of the Anopheles genus. According to data from the World Health Organization (WHO), in 2019, approximately 227 million cases were reported in 85 countries where malaria is endemic. Among the Plasmodium species responsible for human infections, Plasmodium vivax is the most prevalent in Brazil. Malaria treatment is specific to each Plasmodium species and is generally carried out using combination therapies based on artemisinin and quinoline derivatives. These combination therapies aim to minimize the risk of developing parasitic resistance to the employed drugs, although resistance has already been identified. The 8-aminoquinoline substances, primaquine (PQ) or tafenoquine (TQ), along with chloroquine (CQ), are the only currently available drugs for the treatment of Plasmodium vivax malaria. However, individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency should not use PQ or TQ due to the risk of developing severe and potentially fatal hemolytic anemia. Therefore, it is necessary to search for new derivatives for new PQ derivatives to optimize antiplasmodial activity and reduce toxicity. Structural modifications were made to the terminal amine of the alkyl chain of TQ, adding an acetamide group linked to azole heterocycles. Four new derivatives were obtained in satisfactory yields through a simple two-step synthesis route. These derivatives were evaluated in an in vitro model against the Plasmodium falciparum 3D7 strain, but they did not demonstrate significant potency. Cytotoxicity was assessed in human hepatocarcinoma cells, and all derivatives exhibited low toxicity.