title: The antimalarial drugs chloroquine and primaquine inhibit pyridoxal kinase, an essential enzyme for vitamin B6 production.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Shirakawa
authors.affiliation: Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yaoita
authors.affiliation: Institute of Biomedical Innovation, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: First Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagano
authors.affiliation: Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: horiuchi@idac.tohoku.ac.jp.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Horiuchi
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D010966:Plasmodium vivax / Q000201:enzymology; D011319:Primaquine / Q000494:pharmacology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011731:Pyridoxal Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity; D014349:Trypanosoma cruzi / Q000201:enzymology
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D002738:Chloroquine; D011731:Pyridoxal Kinase; D011319:Primaquine
keywords: Chloroquine; Malaria; Primaquine; Pyridoxal kinase