A novel dihydroxylated derivative of artemisinin from microbial transformation
| Autor: | Yulian Zhan, John S. Williamson, Yunpeng Bai, Bo Liu, Yezhi Guan, Yunshan Wu, Fangfang Xu |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Microbial transformation Hydroxylation 01 natural sciences Antimalarials Structure-Activity Relationship Derivative (finance) parasitic diseases Drug Discovery medicine Artemisinin Biotransformation Cunninghamella Pharmacology Cunninghamella elegans Molecular Structure biology 010405 organic chemistry Chemistry General Medicine biology.organism_classification Artemisinins 0104 chemical sciences 010404 medicinal & biomolecular chemistry Dihydroxylation medicine.drug |
| Zdroj: | Fitoterapia. 120:93-97 |
| ISSN: | 0367-326X |
| DOI: | 10.1016/j.fitote.2017.05.015 |
| Popis: | Microbial transformation of artemisinin (1) by Cunninghamella elegans was investigated. Four isolated products were identified as 6β-hydroxyartemisinin (2), 7α-hydroxyartemisinin (3), 7β-hydroxyartemisinin (4), and 6β,7α-dihydroxyartemisinin (5). The structures were elucidated by spectroscopic and X-ray crystallographic analysis. Product 5 is a novel compound and being reported here for the first time. It features two hydroxyl groups in its structure, and this is the first report on dihydroxylation of the artemisinin skeleton. Quantitative structure-activity relationship and molecular modeling studies indicate the modification of artemisinin skeleton will increase antimalarial activity and water solubility. The chemical syntheses of artemisinin derivatives at C6 or C7 position are impossible due to the lack of functional groups. 6β,7α-Dihydroxyartemisinin is hydroxylated at both 6β- and 7α-positions of artemisinin skeleton at the same time. Therefore, this new compound would be a good scaffold for further structural modification in the search for more potent antimalarial drugs. |
| Databáze: | OpenAIRE |
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