Pyronaridine – the Current Antimalarial Standing Up to Parasite Resistance

Pyronaridine, an aza-9-anilinoacridine schizonticide, was synthesized in China 54 years ago and since 2012 has been prescribed globally in combination with artesunate, marketed under the name Pyramax. Artesunate is an analog of artemisinin, a sesquiterpene lactone with an endoperoxide moiety, extracted from Artemisia annua L., and used as an herbal remedy in Chinese traditional medicine to treat jungle fever, also discovered in China at nearly the same time. Pyramax is one of the safest and most efficacious forms of artemisinin combination therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria in adults and children. This narrative review explains the mechanism of action of pyronaridine, why it remains effective against P. falciparum even though the parasite has evolved resistance or tolerance to all other antimalarial drugs used in clinical practice, and suggests possible antiplasmodial deaza-pyronaridine (acridine) analogs that could be used should pyronaridine becomes ineffective.