HIV Latency Reactivation Constituents Research From Euphorbia Peplus

AIDS is an acquired immunodeficiency syndrome caused by human immunodeficiency virus infection.The infective complications caused by the HIV virus have long damaged the patient's body nunctions.The current highly active antiretroviral therapy does not completely eliminate the latent virus reservoir,but with the discovery and in-depth study of the "shock and kill" treatment strategy,it provides the possibility and hope for the complete cure for eliminating latent HIV virus reservoir.The compound PEP005 isolated from Euphorbia peplus has been confirmed to have significant latent HIV reactivation activity,suggesting that the diterpenoids in this plant may have the activity of the reactivation for latent HIV-1 virus.In this research,the compounds isolated and purified from 60%ethanol extracts of the whole grass of E.peplus which growing in Fujian and their activity for reactivation of latent HIV-1 virus reservoir were studied.The silica gel column chromatography,Sephadex LH-20 gel column chromatography,ODS column chromatography,analytical HPLC,semi-preparative HPLC and recrystallization were used to extract the fraction from the 60%ethanol of the plant.18 compounds were isolated from the 95%ethanol eluate fraction of macroporous resin column chromatography,and the structure of the compound was identified by NMR,mass spectrometry,etc.Among the 18 compounds,there are 10 diterpenoids,4 triterpenoids and 4 other types of compounds.Compounds 11%12?13?18 were separated from Euphorbiaceae genus for the first time,and compounds 14?15?16?17 were separated from E.peplus for the first time.Compounds 3?4?7 were isolated as new compounds.In addition,the Jurkat-2D10 cell model was used to study the latent HIV virus reactivition activities of the isolated compounds.The experimental results of the Jurkat-2D10 cell model indicated that compounds 1,2,6,11,and 17 showed obvious reactivation activity for latent HIV virus a in a dose-dependent manner.In addition,further studies have shown that the 5 compounds had significant synergistic effect on the reactivation of latent HIV virus when combined with JQ-1.By analyzing the SAR,it is suggested that the Ingenol skeleton of the diterpenoid may be a structure that plays an important role as a latent HIV virus reactivator,and the hydroxyl group at the C-20 position substituent may enhance its effect.In addition,dihydroflavonoid compound 11 also has good latent HIV reactivation activity.This research provides a chemical basis for further discovery of compounds in the E.peplus,and lays a material foundation for the study of small molecules that reactivate the latent HIV virus and also provides a certain scientific basis for the discovery of latent HIV virus activators.