Natural Phenolic Compounds and Derivatives as Potential Antimalarial Agents

Malaria is a parasitic disease endemic to tropical and subtropical regions responsible for hundreds of millions of clinical cases and hundreds of thousands of deaths yearly. Its agent, the Plasmodium sp., has a highly variable antigenicity, which accounts for the emergence and spread of resistance to all available treatments. In light of this rising problem, scientists have turned to naturally occurring compounds obtained from plants recurrently used in traditional medicine in endemic areas. Ethnopharmacological approaches seem to be helpful in selecting the most interesting plants for the search of new antiplasmodial and antimalarial molecules. However, this search for new antimalarials is complex and time-consuming and ultimately leads to a great number of interesting compounds with a lack of discussion of their characteristics. This review aims to examine the most promising antiplasmodial phenolic compounds (phenolic acids, flavonoids, xanthones, coumarins, lignans, among others) and derivatives isolated over the course of the last 28 y (1990 - 2018) and discuss their structure-activity relationships, mechanisms of action, toxicity, new perspectives they could add to the fight against malaria, and finally, the difficulties of transforming these potential compounds into new antimalarials.