Evaluation of the Activity of 4-Quinolones against Multi-Life Stages of Plasmodium spp

Abstract

Malaria is a critical global health problem, with high mortality and morbidity rates, which ultimately hinder socioeconomic development in endemic areas. The evolution of drug resistance in malaria parasites, particularly in the case of Plasmodium falciparum, and the scarcity of effective drugs both for case management and for blocking transmission contribute to the aggravating malaria's burden. The present study sought to evaluate the potential of novel 4-quinolone derivatives as multistage antimalarials with predicted activity against asexual intraerythrocytic, liver, and transmission-blocking stages. We show that compound 1, a natural 2-substituted-4-quinolone, previously isolated from plants and microorganisms, and its derivatives 2–6, displayed significant activity against Plasmodium sexual stages in both ex vivo and in vivo assays and effectively prevented hepatic cell infections, with compound 1 displaying the highest activity against both sexual and asexual stages. Collectively, we conclude that these compounds warrant further studies toward the development of new antimalarial drugs.