Laboratoire de Chimie des Produits Naturels, UMR CNRS SPE 6134, University of Corsica , 20250, Corte, France.
J Nat Prod. 2014 Jun 27;77(6):1505-12. doi: 10.1021/np500271u. Epub 2014 Jun 13.
Bioassay-guided purification of an EtOAc extract of the whole plant of Euphorbia amygdaloides ssp. semiperfoliata using a chikungunya virus-cell-based assay led to the isolation of six new (1-4, 9, and 10) and six known (5-7, 8, 11, and 12) jatrophane esters. Their planar structures and relative configurations were determined by extensive spectroscopic analysis, and their absolute configurations by X-ray analysis. These compounds were investigated for selective antiviral activity against chikungunya virus (CHIKV), Semliki Forest virus, Sindbis virus, and HIV-1 and HIV-2 viruses. Compound 3 was found to be the most potent and selective inhibitor of the replication of CHIKV and of HIV-1 and HIV-2 (EC50 = 0.76, IC50 = 0.34 and 0.043 μM, respectively). A preliminary structure-activity relationship study demonstrated that potency and selectivity are very sensitive to the substitution pattern on the jatrophane skeleton. Although replication strategies of CHIK and HIV viruses are quite different, the mechanism of action by which these compounds act may involve a similar target for both viruses. The present results provide additional support for a previous hypothesis that the anti-CHIKV activity could involve a PKC-dependent mechanism.
生物测定指导的从 Euphorbia amygdaloides ssp. semiperfoliata 的全植物的 EtOAc 提取物的纯化，使用基孔肯雅病毒细胞测定，导致了六个新的（1-4、9 和 10）和六个已知的（5-7、8、11 和 12）巴豆烷酯的分离。通过广泛的光谱分析确定了它们的平面结构和相对构型，通过 X 射线分析确定了它们的绝对构型。这些化合物被研究了对基孔肯雅病毒（CHIKV）、辛德毕斯病毒、塞姆利基森林病毒和 HIV-1 和 HIV-2 病毒的选择性抗病毒活性。发现化合物 3 是最有效的和选择性的 CHIKV 和 HIV-1 和 HIV-2 复制的抑制剂（EC50 = 0.76、IC50 = 0.34 和 0.043 μM，分别）。初步的构效关系研究表明，效力和选择性对巴豆烷骨架上的取代模式非常敏感。尽管 CHIK 和 HIV 病毒的复制策略有很大的不同，但这些化合物的作用机制可能涉及到两种病毒的类似靶标。目前的结果为以前的假设提供了额外的支持，即抗 CHIKV 活性可能涉及 PKC 依赖性机制。
