title: In silico exploration for agonists/antagonists of brassinolide.
abstract: Brassinolide (BL) is a plant steroid hormone that is necessary for stem elongation and cell division. To date more than 70 steroidal BL-like compounds, which are collectively named as brassinosteroids, have been identified. However, non-steroidal compounds that mimic BL have not been reported yet, which can be used as plant growth regulators. Twenty-two non-steroidal compounds were screened from the database containing about 5 million compound structures using a pharmacophore-based in silico screening method. The crystal structure (PDB: 4LSX) of the BL receptor was used to generate a pharmacophore model required for in silico screening. Among 22 hit compounds, 15 compounds that are thought to be physicochemically acceptable were submitted to the in vivo rice lamina inclination assay. Although no compound showed BL like activity, three compounds were detected as BL antagonist. The most potent compound was an ester derivative of 1,4-diphenlenedimethanol and isoxazole-4-carboxylic acid, and the other two compounds contain 2-phenylfuran and pyrimidin-2(1H)-one moieties bridged by an ethenyl substructure. The 50% effective doses (ED50) for the antagonistic activity were in a range of 0.6-5nmol per plant. The inhibition of the lamina inclination by the most potent agonist was recovered by the co-application of BL in a dose-dependent manner.
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Takimoto
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Airi
authors.initials: A
authors.lastname: Sugiura
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Minami
authors.affiliation: Affinity Science Corporation, Tokyo 107-0052, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Tasaka
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. Electronic address: naka@kais.kyoto-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Miyagawa
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology; D060406:Brassinosteroids / Q000819:agonists* / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology; D000432:Methanol / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D012275:Oryza / Q000187:drug effects / Q000254:growth & development*; D010937:Plant Growth Regulators / Q000737:chemistry* / Q000494:pharmacology; D013260:Steroids, Heterocyclic / Q000819:agonists* / Q000037:antagonists & inhibitors*
chemical_list: D001555:Benzene Derivatives; D060406:Brassinosteroids; D007555:Isoxazoles; D010937:Plant Growth Regulators; D013260:Steroids, Heterocyclic; D000432:Methanol; C023623:brassinolide
keywords: Brassinolide; Brassinosteroids; In silico screening; Pharmacophore; Rice lamina inclination