Studies On The Chemical Constituents And Bioactivities Of Schisandra Bicolor Var.Tuberculata And Pausinystalia Yohimbe

This dissertation consists of three parts.Chapter 1 presents the chemical constituents and biological activities of the fruits and stems of Schisandra bicolor var.tuberculata?Y.W.Law?Y.W.Law,respectively.Chapter 2 describes the chemical constituents and biological activities of the bark of Pausinystalia yohimbe.Chapter 3 is a review about the new alkaloids isolated from the plants in Rubiaceae from 2005 to 2016.Studies on the chemical constituents of the fruits and stems of S.bicolor var.tuberculata and the bark of P.yohimbe led to the isolation of 106 compounds,including 60 lignans,6 triterpenoids,27 alkaloids,2 sesquiterpenoids,2 steroids,2 aliphatics,1 flavonoid,1 phenolic acid and 5 other type compounds.Among these compounds,36 were identified as new compounds.The structures of the isolates were established on the basis of spectroscopic data analysis?1D and 2D NMR,HRESIMS,IR,UV?and by comparison with the published data.The absolute configurations of the new compounds were determined by comparison of the optical rotation and experimental ECD spectra with the similar compounds or comparison of the experimental and calculated ECD spectra or single-crystal X-ray diffraction analysis.Some selected compounds were tested for their in vitro neuroprotective effects or cytotoxic activities or immunosuppressive activities.1.The chemical constituents and biological activities of the fruits and stems of S.bicolor var.tuberculata.Containing two genera Kadsura and Schisandra,Schisandraceae plants have been widely used in traditional Chinese medicine as sedative and tonic agents for a long history.S.bicolor var.tuberculata,a variation belongs to Schisandra,is distributed mainly in Jiangxi,Hunan and Guangxi Provinces of mainland China.Its ripe berries are edible and nutritious,which are eaten by local residents to prevent disease and keep healthy.As a continuation of our previous work,and in order to search for more structurally unique metabolites with promising bioactivities,we investigated the chemical constituents of the fruits and stems of S.bicolor var.tuberculata collected from Xinning County in Hunan Province,China.As a result,25 compounds,including 13 new lignans,were obtained and identified from the fruits of S.bicolor var.tuberculata;and 58 compounds,including 12 new lignans,were isolated and identified from the stems of S.bicolor var.tuberculata.The isolated lignans LF-1?24,LS-1?17,LS-19?26,LS-29?33,LS-35?38 and LS-40 were evaluated for their neuroprotective activities against CoC12-induced hypoxic injury and H2O2,A?25-35-induced oxidative injury in SH-SY5Y cells.All the tested compounds showed neuroprotective effects in these in vitro assays to different degrees.Compounds LF-10,LF-13?14,LF-21?22,LS-3?5,LS-7?8,LS-10,LS-12?13,LS-16,LS-25,LS-31,LS-36,LS-40 in the CoCl₂-induced hypoxic injury model,and compounds LF-2,LF-4,LF-6,LF-8,LF-11?12,LF-16?17,LF-20?21,LS-1,LS-4,LS-6?9,LS-11,LS-19,LS-23?24,LS-31,LS-35?36,LS-40 in the H2O2-induced oxidative injury model,and compounds LF-3-4,LF-6-10,LF-12-17,LF-19,LF-21,LF-23,LS-1,LS-3?4,LS-7?8,LS-14,LS-16,LS-21,LS-23,LS-29,LS-31?32 in the A?25-35-induced oxidative injury assay,improved cell viabilities by more than 15%compared with the negative control group,respectively.Additionally,at the low concentration of 3.2 nM,compounds LF-3,LF-8,LF-9,LF-14?19,LS-2,LS-4?8,LS-23,LS-24,LS-26,LS-35?37,LS-40 in CoCl₂-induced,compounds LF-7,LF-8,LF-13,LF-17,LF-18,LS-4?9,LS-20,LS-23?25,LS-35,LS-37 in H2O2-induced,and compounds LF-2,LF-6,LF-7,LF-9?10,LF-12?19,LS-1?4,LS-7?9,LS-11,LS-14,LS-19,LS-21,LS-23?26,LS-29,LS-31?32,LS-40 in A?25-35-induced SH-SY5Y cell injury models,showed statistically significant neuroprotective activities compared with the negative control group,respectively.Additionally,the isolated triterpenoids LS-41-LS-46 from the stems of S.bicolor var.tuberculata were tested for their in vitro cytotoxic activities against HepG2,MCF7,HT-29 and HeLa cancer cell lines.Compounds LS-42 and LS-43 showed moderate anti-proliferative effects against MCF7 cancer cell line with IC50 values of 49.2 and 47.1 ?M,respectively;Compound LS-42 showed moderate anti-proliferative effect against HeLa cancer cell line with IC50 values of 41.3 ?M.2.The chemical constituents and biological activities of the bark of Pausinystalia yohimbe.Rubiaceae belongs to Order Gentianales,which is an important component of tropical and subtropical flora.Plants in this family,such as Rubia cordifolia,Morinda officinalis,Uncaria rhynchophylla and Cinchona ledgeriana,were widely used in traditional Chinese medicine for their remarkable medicinal functions.The major effective components of these plants are alkaloids,which have been a hot topic in natural product chemistry and drug discovery communities for their novel structures and beneficial pharmacological effects.Some alkaloids derived from Rubiaceae have been widely used in clinical,for example,the anti-malarial quinine isolated from Cinchona ledgeriana and the anti-hypertensive drug rhynchophylline obtained from Uncaria rhynchophylla.Pausinystalia yohimbe is mainly distributed in tropical region of the west coast of Africa.The bark of Pausinystalia yohimbe has been used as aphrodisiac by the local Africans and also for the treatment of fever,leprosy,and cough in the west of Africa.The main chemical constituents in this plant are alkaloids,especially yohimbine and its isomers,which belong to indole alkaloids with wide range of biological activities.In order to search for more structurally unique alkaloids with promising bioactivities and make more efficient use of this plant,we studied the chemical constituents of the bark of Pausinystalia yohimbe as a continuation of our previous work.As a result,27 alkaloids including 12 new analogues were isolated and identified.Selected compounds were evaluated for their in vitro cytotoxic activities against HepG2,MCF7,HT-29 and HeLa cancer cell lines and immunosuppressive activities.Compounds PY-4,PY-14 and PY-15 showed weak anti-proliferative effects against HeLa cancer cell line.Compounds PY-11 and PY-16 exhibited significant inhibition effects with IC50 16.82 ?M and 27.64 ?M against ConA-induced T-cell proliferation,while 13.46 ?M and 40.54 ?M against LPS-induced B-cell proliferation.