title: Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium falciparum cells swell and rupture to death.
abstract: Malaria remains as one of the most devastating infectious disease, and continues to exact an enormous toll in medical cost and days of labor lost especially in the tropics. Effective malaria control and eventual eradication remain a huge challenge, with efficacious antimalarials as important intervention/management tool. Clearly new alternative drugs that are more affordable and with fewer side effects are desirable. After preliminary in vitro assays with plant growth regulators and inhibitors, here, we focus on biosynthetic inhibitors of gibberellin, a plant hormone with many important roles in plant growth, and show their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin biosynthetic inhibitors resulted in marked morphological changes that can be reversed to a certain degree under hyperosmotic environment. These unique observations suggest that changes in the parasite membrane permeability may explain the pleiotropic effects observed within the intracellular parasites.
authors.affiliation: Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka, Suita, Osaka, Japan. toyama-imhp@umin.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyama
authors.forename: Michiru
authors.initials: M
authors.lastname: Tahara
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagamune
authors.forename: Kenji
authors.initials: K
authors.lastname: Arimitsu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamashima
authors.forename: Nirianne M Q
authors.initials: NM
authors.lastname: Palacpac
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaide
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D053898:Biosynthetic Pathways / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology / Q000648:ultrastructure; D005875:Gibberellins / Q000037:antagonists & inhibitors*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D009994:Osmolar Concentration; D021261:Parasitic Sensitivity Tests; D010937:Plant Growth Regulators / Q000037:antagonists & inhibitors*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D013729:Terpenes / Q000032:analysis / Q000378:metabolism
chemical_list: D000962:Antimalarials; D005875:Gibberellins; D010937:Plant Growth Regulators; D013729:Terpenes