title: Synergy of ferrous ion on 5-aminolevulinic acid-mediated growth inhibition of Plasmodium falciparum.
abstract: Haem biosynthesis appeared to be a target of malaria therapy because 5-aminolevulinic acid (ALA), a haem biosynthesis starting material, with light exposure or a high amount of ALA alone reduced Plasmodium falciparum growth to undetectable level. However, the administration of a high dose of ALA is unrealistic for clinical therapy. We found that Fe(2+) enhanced P. falciparum-killing potency of ALA and significantly inhibited the parasite growth. The intermediates of haem biosynthesis localized to the parasite organelles, and coproporphyrin III was the most accumulated intermediate. These novel findings may lead to development of a new anti-malarial drug using ALA and Fe(2+).
authors.affiliation: Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033; Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585, Japan; Department of Biochemistry, Ahmadu Bello University, Zaria 2222, Nigeria; SBI Pharmaceuticals Co, LTD, Izumi Garden Tower 20F, 1-6-1, Roppongi, Minato-ku, Tokyo; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B102 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan; and Division of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Komatsuya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hata
authors.forename: Emmanuel O
authors.initials: EO
authors.lastname: Balogun
authors.forename: Kenji
authors.initials: K
authors.lastname: Hikosaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Ogura
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Sato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kita
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005296:Ferrous Compounds; D000622:Aminolevulinic Acid
keywords: 5-aminolevulinic acid (ALA); Haem synthesis; Plasmodium falciparum; malaria