Synthesis and biological evaluation of novel azole derivatives as selective potent inhibitors of brassinosteroid biosynthesis
| Autor: | Osamu Yajima, Kazuhiro Yamada, Yuko Yoshizawa, Keimei Oh |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Azoles
Stereochemistry Clinical Biochemistry Mutant Arabidopsis Pharmaceutical Science Biochemistry Hydroxylation chemistry.chemical_compound Biosynthesis Brassinosteroids Drug Discovery medicine Molecular Biology chemistry.chemical_classification Molecular Structure biology Organic Chemistry biology.organism_classification Mechanism of action chemistry Molecular Medicine Azole Gibberellin Plant hormone medicine.symptom |
| Zdroj: | Bioorganic & Medicinal Chemistry. 21:2451-2461 |
| ISSN: | 0968-0896 |
| Popis: | Brassinosteroids (BRs) are phytohormones that control several important agronomic traits, such as flowering, plant architecture, seed yield, and stress tolerance. To manipulate the BR levels in plant tissues using specific inhibitors of BR biosynthesis, a series of novel azole derivatives were synthesized and their inhibitory activity on BR biosynthesis was investigated. Structure-activity relationship studies revealed that 2RS, 4RS-1-[4-(2-allyloxyphenoxymethyl)-2-(4-chlorophenyl)-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4]triazole (G(2)) is a highly selective inhibitor of BR biosynthesis, with an IC(50) value of approximately 46 ± 2 nM, which is the most potent BR biosynthesis inhibitor observed to date. Use of gibberellin (GA) biosynthesis mutants and BR signaling mutants to analyze the mechanism of action of this synthetic series indicated that the primary site of action is BR biosynthesis. Experiments feeding BR biosynthesis intermediates to chemically treated Arabidopsis seedlings suggested that the target sites of this synthetic series are CYP90s, which are responsible for the C-22 and/or C-23 hydroxylation of campesterol. |
| Databáze: | OpenAIRE |
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