Studies On MDR-MRSA Inhibitory Components From The Fruits Of Hypericum Sampsonii

Hypericum sampsonii is a perennial herb of Hypericum genus(Hyperiaceae).It has been used as traditional Chinese medicine with the treatment of numerous disorders such as backache, burn,diarrhoea,snakebite and swelling.This plant has been found to have metabolites such as polyisoprenylated benzoylphloroglucinol derivatives,xanthones,flavones and other phenolic principles.It has been discovered that the polyisoprenylated benzoylphloroglucinol derivatives from Hypericum sampsonii showed promising activity against the NorA overexpressing MDR Staphylococcus aureus strain SA-1199B.Staphylococcus aureus is a severe bacterial pathogen which is commonly considered as a major pathogen that causes hospital-acquired infection.In recent years,it has been resistant to a majority of antibiotics.As a result,it is urgent to find new agents to inhibit the multidrug-resistant bacteria.Previously,we have evaluated the activity of the fruits of Hypericum sampsonii against the NorA overexpressing MDR S.aureus strain SA-1199B.Encouraged by its good result,we carried out the phytochemical research on H.sampsonii.On bioassay guided fractionation of ethanol extract for fruits of Hypericum sampsonii,the activity was localized in petroleum ether fraction.Further work led to the isolation of benzoylphloroglucinol derivatives compounds 1-10,including four known compounds(1-4): sampsonione H(1),sampsonione D(2),hypersampsone D(3),sampsonione J(4),and six new compounds(5-10):hypersampsone G(5),hypersampsone H(6),hypersampsone I(7), hypersampsone J(8),hypersampsone K(9) and hypersampsone L(10).These are geranyl bearing caged-sampsonones.There of them were obtained as crystals and their X-ray crystallographes were achieved first time.The experiments on the antibacterial activities of the compounds are ongoing.Compounds hypersampsone G(5) and hypersampsone H(6) were tested for cytotoxicity against human lung adenocarcinoma A549 cells,using the MTT method with etoposide as a positive control.In the bioassay hypersampsone H(6) exhibited marginal inhibitory activity with an IC₅₀ of 120μM,while etoposide showed an IC₅₀ of 7.3μM,whilst hypersampsone G (5) was inactive. This thesis is consisted of three chapters.The first chapter is the preface,in which the research background of antimicrobial resistance in MDR-MRSA was discussed,together with the present research situation of Hypericum genus and Hypericum sampsonii species in the aspects of resources,phytochemistry,and pharmacology.In chapter 2,the isolation, purification and elucidation of the compounds obtained from the fruits of Hypericum sampsonii were discussed,along with the results of cytotoxicity research of compounds hypersampsone G(5) and hypersampsone H(6),and a further discussion of the possible biosynthesis pathway of benzophenone derivatives.The related experimental material and methods as well as the physical and chemical data of the compounds were reported in chapter 3.