Studies On The Secondary Metabolites Of Mangrove Endophytic Actinomycetes And Predicting The Target Of Nature Products By Virtual Screening

Nine plants are collected from the Estuary of BEILUN GUANGXI, including Aegiceras corniculatum, Excoecaria agallocha, Cerbera manghas, Bruguiera gymnorrhiza, Hibiscus tiliaceus, Avicennia marina, Kandelia candel, Clerodendrum inerme, Acrostichum aureum. With strict surface sterilization and controlled trials,11Mangrove endophyte actinomycetes have been isolated by using novobiocin and Trimethoprim. Six ones are from stem and the others are from leavers. Their growth patterns are observed and recorded by fostering. Testing the adaptability of environment is proved. Three of Clerodendrum inerme(KLSJ1、KLSJ2、 KLSY) could grow in the medium salinity and the two endophytic actinomycetes HJJ and MLY could grow without nitrogen which means having the ability of nitrogen fixation.Mangrove grows in the intertidal regime of tropic or subtropics. The special environment makes it having unique metabolism. Actinomycetes play a role in the endophyte, become a significant coming of new nature products. In this paper, according the research of mangrove endophyte actinomycetes and its secondary metabolite, isolation is proved for drug discovery of mangrove resource.According to adjust the kinds of metal ions, different metal ions have different effect about promote or inhibit.0.10g/L Cu2+could promote the LJJ’s growing. The actinomycetes LJJ and KLSY are trained with different culture medium, all are50L. The cultures are filtered and extracted with EA. Dry and smash the thalli and extract by MeOH several times.14compounds are isolated by Si gel and recrystallization. Based on NMR、IR and experiments,11compounds are identified. They are phenylacetic acid(Ⅰ),4-hydroxy-benzoic acid(Ⅱ), Ergosterol(Ⅱ), Vanilline(Ⅳ), Cyclo(Gly-Pro)(Ⅴ), Heptadecanoic acid(Ⅶ), Nonadecanoic acid(Ⅷ), Ergosta-7,22-dien-3β,5α,6β-triol(Ⅸ), Peroxy ergosterol(Ⅺ), Mannitol(Ⅺ) and Sorbitol(Ⅻ).The isolation proved that the addition of Cu2+change the metabolic pathways and be helpful for Aromatics synthetizing.Natural products are the important data base of drug discovery, because their better activity and less toxicity. So that many lead compounds have fund. But the development of pharmacology is slow down as the reasons of sources and getting little. The efficacies of nature products have been prove that play the role in the treatment having function of multi-ligent/target. Founding new lead compounds and illustrating the mechanism of nature products are research focus.I introduce the mode for virtual screening by forward-docking and reward-docking technology. Founding the leading compounds though the virtual screening of the second metabolites in endophytes of Mangrove Siraitia grosvenori and the Guben Zhike Electurary to elaborate the mechanism of nature products.Ten active ingredients are fund in the second metabolites of Mangrove endophytes. Two BcI-XL inhibitors(compound8and32) have activity in anti-tumour, as well as anti-inflammation、anti-biosis and anti-viral. Caspase-8plays an important role in the mechanism of apoptosis controlling by the BcI-XL. Compound8and32have strongly interaction with it which is also elaborate the molecular collaborative antagonism mechanism. Lay the foundation of drug discovery from lead compounds.Among the ten active ingredients from the secondary metabolites of Siraitia grosvenori endophytes, each one has strongly interaction with a series of related enzyme(GSTs、 CYP450、ADH and ChE)in drug metabolizing. Because of stimulate with outside, the enzymes are drug-fast. The inhibition of active ingredients means the potential of drug discovery in anti-drug-fast. Provide a new way for modern development of Siraitia grosvenon.In the research of Zhuang Medicine Guben Zhike Electurary by virtual screening,19active ingredients are fund, as well as the targets. Elaborate the coordination among medicinal materials. Meanwhile the traditional effect is illustrated, which include the aspects about anti-inflammation、anti-biosis and anti-viral. It contributes to improve the security of drug with illustrating the toxicity. Provide new strategies of modern development of Compound of Zhuang Medicine at the same time.