A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study
| Autor: | Kailong Ji, Wei Liu, Weihang Yin, Xiangrong Kong, Honghong Xu, Zeng-Wei Lai, Jing-Ya Li, Jian-Min Yue |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Acta Pharmaceutica Sinica B, Vol 13, Iss 8, Pp 3414-3424 (2023) |
| Druh dokumentu: | article |
| ISSN: | 2211-3835 70941718 |
| DOI: | 10.1016/j.apsb.2023.05.001 |
| Popis: | A new class of potent liver injury protective compounds, phychetins A−D (1−4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2−4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1−4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel–Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2−4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent. |
| Databáze: | Directory of Open Access Journals |
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