Studies On The Constituents From Garcinia Lancilimba,Agelas Sp.,and Aspergillus Terreus And Their Biological Activities

The natural products from the terrestrial plants,marine benthic and its symbiotic microorganisms have chemical and function diversity,which provide a unique infrastructure resource for the development of innovative drugs.Most clinical drugs are derived from the design and modification of natural products and their derivatives.The scientists have been committed to search for potential drug compounds with unique structure and good biological activity from the natural products.Chemical investigation on Garcinia lancilimba,Agelas sp.,and Aspergillus terreus by various chromatographic methods led to the isolation and structure determination of 72 compounds.Among these compounds,10 of them were new compounds.Their structures were elucidated on the basis of physico-chemical data,spectroscopic analyses(UV,IR,MS,NMR,OR),and electronic circular dichroism calculation.Most of the compounds were evaluated for cytotoxic,antibacterial,antioxidant,acetylcholinesterase inhibitory,and α-glucosidase inhibitory activities.G.lancilimba,an arbor belonging to the family of Guttiferae,is mainly distributed in the southeast of Yunnan province in China.Garcinia plants were used as folk medicine for a long history with anti-inflammatory activity.Modern pharmacology study shows that these plants have anti-tumor,antioxidant,antibacterial,anti-inflammatory and other pharmacological activities.23 compounds from the 95%ethanol extract of the G.lancilimba were obtained by chromatographic methods including open silica gel,ODS,Sephadex LH-20 column chromatography,and semi-preparative HPLC.These structures were categorized as 18 xanthones,2 flavonoids,2 biflavonoids,and one tocotrienol.They were identified as garcinexanthones G-1(A3,A1-A2),xanthone V1(A4),xanthone V1a(A5),1,5,6-trihydroxy-6’,6’-dimethyl-2H-pyrano(2’,3’:3,4)-2-(3-methylbut-2-enyl)xanthone(A6),4-(3’,7’-dimethylocta-2’,6’-dienyl)-1,3,5-trihydroxy-9H-xanthen-9-one(A7),gerontoxanthone C(A8),dulxanthone A(A9),1,3,5,6-tetrahydroxy-4-prenylxanthone(A10),jacareubin(All),isojacareubin(A12),isocudraniaxanthone A(A13),2-deprenylrheediaxanthone B(A14),1,5,6-trihydroxy-3-methoxyxanthone(A15),1,5,6-trihydroxy-3,7-dimethoxyxanthone(A16),1,7-dihydroxyxanthone(A17),gentisin(A18),kaempferol(A19),5,7-dihydroxy-6,4’-dimethoxyflavone(A20),pancibiflavonol(A21),morelloflavone(A22),and litchtocotrienol A(A23).All of the xanthones were evaluated for their cytotoxic activity against HL-60(human leukemia),A549(human lung cancer),and MCF-7(human breast cancer)cell lines.Compound A5 with two prenyls was the most effective against the HL-60 cell line with IC50 values of 1.68 μM,while compounds A16 and A11 exhibited the highest activity against A549 and MCF-7 cells with IC50 values of 4.88 and 6,28 μM,respectively.Agelas sp.belongs to class Demospongiae,order Agelasida,family Agelasidea,which has proven to be a rich source of monomeric and dimeric bromopyrrole alkaloids,diterpene alkaloids with antibacterial,cytotoxic,antimalarial,and immunomodulatory activities.By various chromatographic methods such as VLC,MPLC,Sephadex LH-20,and HPLC,16 compounds were isolated including four new dimeric bromopyrrole alkaloids,nine monomeric bromopyrrole alkaloids,and others.They were identified as hexazosceptrin(B1),agelestes A-B(B2-B3),(9S,10R,9’S,10’R)-nakamuric acid(B4),(-)-monobromophakellin(B5),(-)-dibromophakellin(B6),aldisin(B7),2-bromoaldisin(B8),4,5-dibromopyrrole-2-carboxylic acid(B9),4,5-dibromopyrrole-2-carboxamide(B10),4-bromopyrrole-2-carboxylic acid(B11),5-bromopyrrole-2-carboxamide(B12),pyrrole-2-carboxylic acid(B13),thymine(B14),2’-deoxythymidine(B15),and 3,7-dimethylguanin-1/3-ium(B16).The new compounds B1-B4 were evaluated for antibacterial activity against human pathogenic bacteria,including Escherichia coli ATCC25922,methicillin-sensitive Staphylococcus aureus ATCC25923,and methicillin-resistant S.aureus ATCC43300,Compounds B1 and B4 exhibited moderate activities against S.aureus ATCC25923 and S.aureus ATCC43300 with the same MIC value of 16μg/mL.Aspergillus terreus 152805 was isolated from marine sponge Phakellia fusca.After the fermentation,ethyl acetate extraction,and systematically isolation,33 compounds were obtained by chromatographic methods including VLC,MPLC,Sephadex LH-20,and HPLC.Their structures were identified as(-)-asperteretal D(C1),(+)-asperteretal D(C2),asperteretal E(C3),(±)flavipesolide C(C4),(±)flavipesolide B(C5),butyrolactone Ⅰ(C6),butyrolactone Ⅱ(C7),5-[(3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-3-hydroxy-4-(4-hydroxyphenyl)-2(5H)-furanone(C8),aspernolide A(C9),butyrolactone Ⅳ(C10),butyrolactone Ⅴ(C11),aspulvinone E(C12),asterrelenin(C13),acetylaszonalenin(C14),territrem B(C15),territrem C(C16),acetylapoaranotin(C17),acetylaranotin(C18),alternarosin A(C19),methyl 3,4,5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate(C20),terrelumamide A(C21),emeheterone(C22),(8R,9S)-dihydroisoflavipucine(C23),(8S,9S)-dihydroisoflavipucine(C24),cyclo(S-Pro-S-Phe)(C25),brevianamide F(C26),de-O-methyldiaporthin(C27),4-hydroxykigelin(C28),cis-4,6-dihydroxymellein(C29),6,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin(C30),3-methyl-6-hydroxy-8-methoxy-3,4-dihydroisocoumarin(C31),6,8-dimethoxy-3-methyl-3,4-dihydroisocoumarin(C32),terrain(C33).Compounds C1,C6,C26,and C28 exhibited moderate DPPH radical scavenging capacity with IC50 values of 60,86,90,and 38 μg/mL,respectively.In addition,compounds C1-C9,C11,C13,and C22 showed potent inhibitory activity against α-glucosidase with IC50 values of 9.98,8.65,13.36,20.3,7.63,14.18,85.13,11.65,47.33,110.27,74.35,14.28 μM,respectively.Compounds C15 and C16 showed strong acetyl cholinesterase inhibitory activity with IC50 values of 13.54 and 16.68 nM,respectively.