Investigation On Bioactive Constituents Of Three Plants And One Endophytic Fungus

Natural products are important sources for new drug research and development.A large number of novel natural compounds with significant pharmacological activities have been reported from the genera of Cinnamomum and Viburnum and endophytic fungi Pestalotiopsis.Therefor,it's worthy studying the medicinal plants and fungi of same genera to discover more novel and bioactive compounds for further drug research and development.In this paper,three medicinal plants,Cinnamomum bejolghota,Cinnamomum mollifolium and Viburnum brachybotryum,and an endophytic fungus,Pestalotiopsis flavidula,have been studied systematically on their chemical constituents and bioactivities.Ninety-four pure compounds,including forty-two new compounds,were obtained by using many kinds of chromatographic techniques,and the structures were identified by spectroscopic techniques and classified as lignans,phenylpropanoids,iridoids,spiroketals,sesquiterpenoids,and so on.In addition,all the isolates were evaluated for their antitumor and antioxidant activities with MTT method and DPPH assay,respectively.In the first chapter,79 compounds,including 31 new compounds,were isolated from leaves and twigs of Cinnamomum bejolghota,and Cinnamomum mollifolium,and an endophytic fungus Pestalotiopsis flavidula isolated from Cinnamomum camphora branches.Amongst,30 compounds were isolated from C.bejolghota,classified as 21lignans or neolignans(1-21),8 flavonoids(22-29)and a sesquiterpenoid(30),including 4 new neolignans named bejolghotin A-D(1-4)and 3 new lignans bejolghotin E-G(compounds 9-11).46 compounds were isolated from C.mollifolium,including 22 new compounds classified as 9 new lignans mollifolenides A-I(31-36 and45-47),6 pairs of phenylpopanoid enantiomers(±)-mollifolins A-F(49a/49b-54a/54b)and a new sesquiterpene Mollifolins G(65).These 6 pairs of enantiomers with the sanme formula and two chiral centers were successfully purified by chiral HPLC resolution to yield 12 optically pure compounds,four for each of three kinds of planar structures.Interestingly,the amount of each pair of enantiomers is almost equal,which is extremely rare in the nature,and worthy to be studied for the biosynthesis and non-stereoselectivity of natural products.Furthermore,all the islateds from C.bejolghota and C.mollifolium were evaluated for their anticancer activity against three human cancer cell lines(A549,MDA-MB-231and HCT-116).The results revealed that compounds 11-13 showed significant activity with IC₅₀ values of 0.78-2.93?M.while compounds 1-3 had moderate activity.Moreover,all the isolates from C.bejolghota were tested for antioxidant activity in DPPH assay and 20 compounds displayed comparable activity with the positive controls,which confirmed its health benefits.Three spiroketal derivatives(71-73)were isolated by the aytotoxicity-guided separation and elucidated from the endophytic fungus Pestalotiopsis flavidula,including 2 new ones 2(?)-aminodechloromaldoxin(71)and 2(?)-aminodechlorogeodoxin(72),bearing a-NH₂ group.And then 3 compounds were evaluated in vitro for anti-cancer activity against a panel of human cancer cell lines and the results showed 71and 72 with moderate cytotoxicity while 73 was inactive,which suggested-NH₂ group might play a very important role for their cytotoxicity.In the second chapter,15 compounds,11 new iridoids brachybone A-K(74-84)and 4 known terpenoids,were isolated and characterized from Viburnum brachybotryum.All the 11 iridoids beared a rare carbonyl at C-7,and furthermore brachybones A-C(74-76)contained an unprecedented chlorine atom in their structures,which is the first time to be reported from Viburnum genus to the best of our knowledge.In addition,unique oxygen bridge rings were discovered in compounds 83 and 84.Compounds 74and 79 showed moderate inhibitory effect against HCT-116 cell with IC₅₀ value of 16.1?m and 26.6?m,respectively,when evaluated for the anticancer activity of all the isolates.