Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments

Abstract

Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites. Due to the high complexity of the parasite’s life cycle, we partly depend on antimalarial drugs to fight this disease. However, the emergence of resistance, mainly by Plasmodium falciparum, has dethroned most of the antimalarials developed to date. Given recent reports of resistance to artemisinin combination therapies, first-line treatment currently recommended by the World Health Organization, in Western Cambodia and across the Greater Mekong sub-region, it seems very likely that artemisinin and its derivatives will follow the same path of other antimalarial drugs. Consequently, novel, safe and efficient antimalarial drugs are urgently needed. One fast and low-cost strategy to accelerate antimalarial development is by recycling classical pharmacophores. Quinacrine, an acridine-based compound and the first clinically tested synthetic antimalarial drug with potent blood schizonticide but serious side effects, has attracted attention due to its broad spectrum of biological activity. In this sense, the present review will focus on efforts made in the last 20 years for the development of more efficient, safer and affordable antimalarial compounds, through recycling the classical quinacrine drug.