Antimalarial eudesmane sesquiterpenoids from Dobinea delavayi
来源:本地 作者:肖朝江 发布时间:2020-06-08 20:13 点击次数:
Eleven new angeloylated eudesmane sesquiterpenoids, dobinins D–N (2, 3, 5, 6, 8, 9, and 11–15), and four known compounds (1, 4, 7, and 10) were isolated from the roots of Dobinea delavayi. A new oxidation product (8a) was also obtained from dobinin H (8). Their structures were elucidated by spectroscopic data and single-crystal X-ray diffraction analyses. Dobinins K–N (12–15) are the first examples of rearrangement noreudesmane analogue sesquiterpenoids with a unique 6/5-fused carbon skeleton. A putative biosynthetic pathway of compounds 12–15 is proposed. Compound 12 exhibited significant antimalarial activity superior to artemisinin with the inhibition ratio of 59.1%, and compounds 3, 5, and 15 exhibited moderate antimalarial activities against Plasmodium yoelii BY265RFP with inhibition ratios ranging from 14.5% to 18.5% at a dose of 30 mg/kg/day. In addition, the apoptosis of P. yoelii BY265RFP by the depolarization of mitochondrial membrane potential with striking ROS production, after parasitized erythrocyte lysis mediated by cytokines IL-12 and IFN-γ, may be a possible mechanism of antimalarial action of compound 12 against P. yoelii BY265RFP.(全文链接)
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