Total synthesis and anti-inflammatory evaluation of violacin A and its analogues
| Autor: | Qingyin Liu, Minjuan Xu, Jun Xu, Jian Ma, Xueshi Huang, Jiali Xun, Wenxi Wu, Qi An, Li Han, Yu Mu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Molecular Structure
010405 organic chemistry Chemistry Stereochemistry medicine.drug_class Organic Chemistry Anti-Inflammatory Agents Substituent Total synthesis Regioselectivity Cyclotides Orcinol 01 natural sciences Biochemistry Anti-inflammatory 0104 chemical sciences Nitric oxide Acylation 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Drug Discovery medicine Humans Hemiacetal Molecular Biology |
| Zdroj: | Bioorganic Chemistry. 94:103420 |
| ISSN: | 0045-2068 |
| Popis: | A concise total synthesis of an exceedingly potent anti-inflammatory agent violacin A as well as the preparation of thirty analogues of this lead from commercially available orcinol are described. Highlights of our synthetic efforts involve Friedel-Crafts acylation, the regioselective etherification and esterification of phenolic hydroxyl groups, and Baker-Venkatamaran rearrangement to form basic skeleton of violacin A. The deprotection reaction with Pd-catalytic was involved to avoid the elimination of the hemiacetal hydroxyl at C2. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO) production using lipopolysaccharide (LPS)-induced Raw264.7 cells. A range of violacin A derivatives 11b, 11d, 11f, 12e, 12g, 13g, 17d-g exhibited stronger anti-inflammatory effect than that of violacin A. Notably, halogeno-benzyloxy substituent at C-7 were favourable for anti-inflammatory activities of violacin A derivatives. Additionally, Western blot results indicated halogeno-benzyloxy derivatives inhibited pro-inflammatory cytokines releases correlated with the suppression of NF-κB signaling pathway. |
| Databáze: | OpenAIRE |
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