The antimalarial drugs chloroquine and primaquine inhibit pyridoxal kinase, an essential enzyme for vitamin B6 production

•Quinoline derivatives, chloroquine and primaquine are used as antimalarial drugs.•Human pyridoxal kinase was identified as a binding protein of primaquine.•Primaquine inhibited pyridoxal kinases of malaria, trypanosome and human.•Chloroquine inhibited malaria pyridoxal kinase, but not human and trypanosome ones.•Pyridoxal kinase could be a target of antimalarial and adverse effects of the drugs. Quinoline derivatives such as chloroquine and primaquine are widely used for the treatment of malaria. These drugs are also used for the treatment of trypanosomiasis, and more recently for cancer therapy. However, molecular target(s) of these drugs remain unclear. In this study, we have identified human pyridoxal kinase as a binding protein of primaquine. Primaquine inhibited pyridoxal kinases of malaria, trypanosome and human, while chloroquine inhibited only malaria pyridoxal kinase. Thus, we have identified pyridoxal kinase as a possible target molecule of the antimalarial drugs chloroquine and primaquine.