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The drug is used in combination with artesunate for the treatment of uncomplicated <jats:italic>P. falciparum<\/jats:italic> malaria, in adults and children. The present review briefly retraces the discovery of PYR and recent antimalarial studies which has led to the approval of PYR\/artesunate combination (Pyramax) by the European Medicines Agency to treat uncomplicated malaria worldwide. PYR also presents a marked antitumor activity and has revealed efficacy for the treatment of other parasitic diseases (notably <jats:italic>Babesia<\/jats:italic> and <jats:italic>Trypanosoma<\/jats:italic> infections) and to mitigate the Ebola virus propagation. On the one hand, PYR functions has an inhibitor of hemozoin (biomineral malaria pigment, by\u2010product of hemoglobin digestion) formation, blocking the biopolymerization of \u03b2\u2010hematin and thus facilitating the accumulation of toxic hematin into the digestive vacuole of the parasite. On the other hand, PYR is a bona fide DNA\u2010intercalating agent and an inhibitor of DNA topoisomerase 2, leading to DNA damages and cell death. Inhibition of hematin polymerization represents the prime mechanism at the origin of the antimalarial activity, whereas anticancer effects relies essentially on the interference with DNA metabolism, as with structurally related anticancer drugs like amsacrine and quinacrine. In addition, recent studies point to an immune modulatory activity of PYR and the implication of a mitochondrial oxidative pathway. An analogy with the mechanism of action of artemisinin drugs is underlined. In brief, the biological actions of pyronaridine are recapitulated to shed light on the diverse health benefits of this unsung drug.<\/jats:p>","DOI":"10.1002\/bip.23398","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T10:48:34Z","timestamp":1601203714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Pyronaridine: An update of its pharmacological activities and mechanisms of action"],"prefix":"10.1002","volume":"112","author":[{"given":"Christian","family":"Bailly","sequence":"first","affiliation":[{"name":"OncoWitan  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"736","volume":"14","author":"Zheng X. Y.","year":"1979","journal-title":"Yao Xue Xue Bao"},{"key":"e_1_2_12_3_1","first-page":"118","volume":"17","author":"Zheng X. 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