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Preparation And Bioactivity Evaluation Of Huperzine A Derivatives By Biotransformation Of Endophytic Fungi From Huperzia Serrata

Posted on:2019-10-13Degree:MasterType:Thesis
Country:ChinaCandidate:C X ZhangFull Text:PDF
GTID:2404330596464750Subject:Pharmacy
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Microbial transformation has been proved to be an effective method in the structural modification of natural products.The development of new microbial resources is of vital importance to increase the diversities of the transformation reaction types and the structural diversities of the transformed products.With the aim of enriching the structural diversities of the host plants,the present study tried to explore in the endophytic fungi for the microorganisms with the ability to transform the constituents of their host plant.A total of 120 strains of endophytic fungi were isolated from the medicinal plants Huperzia serrata.In the preliminary screening,two strains ZJUT-HS28 and ZJUT-HS39 were found to possess the ability of transforming the two representative alkaloids of the host plant H.serrata i.e.huperzine A and B(hupA and hupB),and were identified as Bjerkandera sp.and Irpex lacteus,respectively.In the subsequent study,two compounds 1 and 2 were isolated and identified from the transformation system of Irpex lacteus ZJUT-HS39.Among them,compounds 1-2 were diastereoisomers with new structure originated from hupA.In addition,five compounds 3-7 were isolated and identified from the transformation system of Bjerkandera sp.ZJUT-HS28.Compound 3 was deduced to possess a new structure of Hup B 8?,15?-epoxide.While compound 4 was identified as Hup A 8?,15?-epoxide with only two previous reports,both of which had been derived from microbial transformation.In the fourth chapter,anti-neurergic inflammatory activity of the isolated transformation products was evaluated.Compound 1 and 2 had exihibited potent anti-inflammatory activity and significantly increased the survival rate of astrocytes induced by LPS.The results laid the foundation for further investtigations on the neuroprotective effect of hup A derivatives.The results of this study supported the use of fungal endophytes as biocatalysts for the biotransformation of natural products,particularly those originating from the host plant.
Keywords/Search Tags:Huperzia serrata, endophytic fungi, biotransformation, huperzine A, huperzine B
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