In silico exploration for agonists/antagonists of brassinolide
| Autor: | Airi Sugiura, Yoshiaki Nakagawa, Seisuke Takimoto, Saki Minami, Hisashi Miyagawa, Tomohiko Tasaka |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Agonist Stereochemistry medicine.drug_class medicine.medical_treatment In silico Clinical Biochemistry Protein Data Bank (RCSB PDB) Pharmaceutical Science 01 natural sciences Biochemistry 03 medical and health sciences chemistry.chemical_compound Steroids Heterocyclic Plant Growth Regulators In vivo Brassinosteroids Drug Discovery Benzene Derivatives medicine Computer Simulation Receptor Molecular Biology Brassinolide 010405 organic chemistry Methanol Organic Chemistry Oryza Isoxazoles 0104 chemical sciences Steroid hormone 030104 developmental biology chemistry Molecular Medicine Pharmacophore |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:1709-1714 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.02.054 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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