New neolignans that inhibit DNA polymerase beta lyase

Bioassay-directed fractionation of a methyl ethyl ketone extract of the roots of Endlicheria aff. resulted in the isolation of four new neolignans (1-4) and eight known compounds, namely, canellin A (5), canellin C (6), 3'-methoxyguianin (7), (7S,8R,1'S,5'S,6'R)-Delta(2',8')-3',6'-dihydroxy-5'-methoxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan (8), armenin-B (9), dillapiole (10), 1-allyl-2,6-dimethoxy-3,4-methylenedioxybenzene (11), and omega-hydroxyisodillapiole (12). The structures of the new compounds (1-4) were established as (7S,8R,1'S,5'S,6'R)-Delta(2',8')-5',6'-dihydroxy-3'-methoxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan, (7S,8R,1'S,5'S,6'R)-Delta(2',8')-3',5',6'-trihydroxy-3,4-methylenedioxy-4'-oxo-8.1',7.5'-neolignan, 2,4-dimethoxy-5,6-methylenedioxy-1-(2-propenyl)benzene, and 2,6-dimethoxy-3,4-methylenedioxycinnamyl alcohol, respectively, on the basis of spectroscopic interpretation.     

Bioactive secondary metabolites from Boesenbergia pandurata of Myanmar and their preferential cytotoxicity against human pancreatic cancer PANC-1 cell line in nutrient-deprived medium

The chloroform extract of rhizomes of Boesenbergia pandurata demonstrated marked preferential cytotoxicity against human pancreatic PANC-1 cancer cells in nutrient-deprived medium. Bioactivity-directed investigation of this extract yielded four new secondary metabolites, geranyl-2,4-dihydroxy-6-phenethylbenzoate ( 1), 2',4'-dihydroxy-3'-(1'-geranyl)-6'-methoxychalcone ( 2), (1' R,2' S,6' R)-2-hydroxyisopanduratin A ( 3), and (2 R)-8-geranylpinostrobin ( 4), and twenty known compounds ( 5- 24). Among the known compounds, (2 S)-6-geranylpinostrobin ( 5), (+/-)-6-methoxypanduratin A ( 6), and (2 S)-7,8-dihydro-5-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-8-phenyl-2 H,6 H-benzo[1,2- b:5,4- b']dipyran-6-one ( 7) were isolated for the first time from a natural source. The structures of these compounds were elucidated using extensive spectroscopic techniques including CD measurements. All the isolated compounds showed varying degrees of in vitro preferential cytotoxicity against PANC-1 cells. Nicolaioidesin B ( 11) and panduratin A ( 17) were most potent, each showing a PC 100 at 2.5 microM.     

Antifungal flavonoids from Hildegardia barteri

A new isoflavan, (3R)-6,2'-dihydroxy-7-methoxy-4',5'-methylenedioxyisoflavan, hildegardiol (1), and two known flavonoids, 2-hydroxymaackiain (2) and farrerol (3), were isolated from the antifungal root extract of Hildegardia barteri. The pterocarpan 2 was largely responsible for the observed antifungal activity.     

Benzoic acid derivatives, acetophenones, and anti-inflammatory constituents from Melicope semecarpifolia

Two new benzoic acid derivatives, (E)-3-acetyl-6-(3,7-dimethylocta-2,6-dienyloxy)-2,4-dihydroxybenzoic acid (1) and (E)-3-acetyl-4-(3,7-dimethylocta-2,6-dienyloxy)-2,6-dihydroxybenzoic acid (2), and three new acetophenones, (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2,2-dimethyl-2 H-chromen-8-yl)ethanone (3), (E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-7-hydroxy-2-methyl-2-(4-methylpent-3-enyl)-2 H-chromen-8-yl)ethanone (4), and (R,E)-1-(5-(3,7-dimethylocta-2,6-dienyloxy)-3,7-dihydroxy-2,2-dimethylchroman-8-yl)ethanone (5), have been isolated from the fruits of Melicope semecarpifolia, together with eight known compounds. The structures were determined through in-depth NMR and mass spectrometric analyses. Among the isolated compounds, 2-(1'-geranyloxy)-4,6,beta-trihydroxyacetophenone (8), 4-(1'-geranyloxy)-2,6,beta-trihydroxyacetophenone (9), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (10), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (11), and 5,4'-dihydroxy-3,7-dimethoxyflavone (12) exhibited potent inhibition (IC50<4 microg/mL) on superoxide anion generation and elastase release by human neutrophils in response to fMet-Leu-Phe/cytochalasin B.     

5-deoxyflavones with cytotoxic activity from Mimosa diplotricha

Bioassay-guided isolation of Mimosa diplotricha led to the isolation of four new 5-deoxyflavones, diplotrins A-C (1-3) and diplotasin (4), together with 12 known flavonoids, flavonolignans, and triterpenoids. On the basis of spectroscopic evidence, compounds 1-4 were characterized as 2',5'-dihydroxy-3,7,8,4'-tetramethoxyflavone (1), 3'-hydroxy-3,7,8,4'-tetramethoxyflavone (2), 2'-hydroxy-7,4',5'-trimethoxyflavone (3), and 4-hydroxy-3,10,11-trimethoxyisochromeno-[4,3-b]-chromen-7(5H)-one (4). The cytotoxic effects of these isolated compounds were evaluated against the A549, AGS, HT-29, and PC3 human cancer cell lines. Compounds 2 and 5″-methoxyhydnocarpin-D (5) showed the most potent antiproliferative activity.     

Antifibrotic phenanthrenes of Dendrobium nobile stems

Two new phenanthrenes ( 1 and 6) and four new dihydrophenanthrenes ( 2- 5) were isolated from a methanolic extract of Dendrobium nobile stems, along with 13 known phenanthrenes and dihydrophenanthrenes ( 7- 19). By spectroscopic analysis, the structures of compounds 1- 6 were determined as 2,8-dihydroxy-3,4,7-trimethoxyphenanthrene ( 1), 3-hydroxy-2,4,7-trimethoxy-9,10-dihydrophenanthrene ( 2), 2,8-dihydroxy-3,4,7-trimethoxy-9,10-dihydrophenanthrene ( 3), 2-hydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene ( 4), 2,2'-dihydroxy-3,3',4,4',7,7'-hexamethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene ( 5), and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene ( 6), respectively. Antifibrotic activity of compounds 1- 19 was evaluated employing HSC-T6, an immortalized rat hepatic stellate cell line, as an in vitro assay system by assessing cell proliferation.     

兴安黄芪化学成分研究

目的:研究兴安黄芪的化学成分。方法:用硅胶柱色谱、重结晶及半制备HPLC进行分离纯化,根据理化性质和光谱数据进行结构鉴定。结果:得到6个单体化合物,分别为7,2′-二羟基-3,′4′-二甲氧基异黄烷(1),2′-羟基-3,′4′-二甲氧基异黄烷-7-O--βD-葡萄糖苷(2),8,2′-二羟基-7,4′-二甲氧基异黄烷(3),7-羟基-4′-甲氧基异黄酮(4),7,3′-二羟基-4′-甲氧基异黄酮(5),9,10-二甲氧基紫檀烷-3-O--βD-葡萄糖苷(6)。结论:这些化合物均系首次从该植物中得到。     

Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata

Six newphenanthrene derivatives, including three monophenanthrenes (1-3), two biphenanthrenes (4 and 5), and a triphenanthrene (6), have been isolated from an ethanolic extract of the tubers of Cremastra appendiculata. Using spectroscopic methods, the structures of compounds 1-6 were determined as 1-hydroxy-4,7-dimethoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (1), 1,7-dihydroxy-4-methoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (2), 2-hydroxy-4,7-dimethoxyphenanthrene (3), 2,7,2'-trihydroxy-4,4',7'-trimethoxy-1,1'-biphenanthrene (4), 2,2'-dihydroxy-4,7,4',7'-tetramethoxy-1,1'-biphenanthrene (5), and 2,7,2',7',2' '-pentahydroxy-4,4',4' ',7' '-tetramethoxy-1,8,1',1' '-triphenanthrene (6), respectively. Compounds 1-6 and two known compounds, cirrhopetalanthin (7) and flavanthrinin (8), obtained previously from this plant, were evaluated against six human cancer cells and a normal cell line.     

Biphenyl glycosides from the fruit of Pyracantha fortuneana

Five new biphenyl glycosides, fortuneanosides A (1), B (2), C (3), D (4), and E (5), were isolated from the fruit of Pyracantha fortuneana. Their structures were established as 3,3'-dihydroxy-5'-methoxy-(1,1'-biphenyl)-4-O-beta-d-glucoside, 4'-hydroxy-2,3',5'-trimethoxy-(1,1'-biphenyl)-2'-O-beta-d-glucoside, 4'-hydroxy-3',5'-dimethoxy-(1,1'-biphenyl)-2-O-beta-d-glucoside, 2,4'-dihydroxy-3',5'-dimethoxy-(1,1'-biphenyl)-3-O-beta-d-glucoside, and 3,4'-dihydroxy-3',5'-dimethoxy-(1,1'-biphenyl)-4-O-beta-d-glucoside by spectroscopic analysis. All compounds were evaluated for inhibitory activity against tyrosinase. Compared with arbutin (IC(50) = 0.23 mM), fortuneanoside D possessed more potency, with an IC(50) value of 0.07 mM.     

Aromatase inhibitors from Broussonetia papyrifera.

Bioassay-guided fractionation of an ethyl acetate-soluble extract from the whole plants of Broussonetia papyrifera, using an in vitro aromatase inhibition assay, led to the isolation of five new active compounds, 5,7,2',4'-tetrahydroxy-3-geranylflavone (1), isogemichalcone C (8), 3'-[gamma-hydroxymethyl-(E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate (9), demethylmoracin I (10), and (2S)-2',4'-dihydroxy-2' '-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanone (11), and 10 known (12-21) compounds which were also found to be active. Of these compounds, the most potent were 9 (IC(50) 0.5 microM), 11 (IC(50) 0.1 microM), isolicoflavonol (12, IC(50) 0.1 microM), and (2S)-abyssinone II (13, IC(50) 0.4 microM). Additionally, six new compounds, 5,7,3',4'-tetrahydroxy-6-geranylflavonol (2), 5,7,3',4'-tetrahydroxy-3-methoxy-6-geranylflavone (3), (2S)-7,4'-dihydroxy-3'-prenylflavan (4), 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propane (5), 1-(2,4-dihydroxy-3-prenylphenyl)-3-(4-hydroxyphenyl)propane (6), and 1-(4-hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane (7), were isolated and characterized, but proved to be inactive as aromatase inhibitors, as were an additional 21 known compounds. The structures of the new compounds (1-11) were elucidated by spectroscopic methods. Structure-activity relationships in the aromatase assay were determined for the benzofurans, biphenylpropanoids, coumarins, and various types of flavonoids (chalcones, flavans, flavanones, and flavones) obtained among a total of 42 constituents of B. papyrifera.     

Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima

Four new terpenylated coumarins (1-4) were isolated from the stem bark of Ailanthus altissima by bioactivity-guided fractionation using an in vitro SIRT1 deacetylation assay. Their structures were identified as (2'R,3'R)-7-(2',3'-dihydroxy-3',7'-dimethylocta-6'-enyloxy)-6,8-dimethoxycoumarin (1), 6,8-dimethoxy-7-(3',7'-dimethylocta-2',6'-dienyloxy)coumarin (2), (2'R,3'R,6'R)-7-(2',3'-dihydroxy-6',7'-epoxy-3',7'-dimethyloctaoxy)-6,8-dimethoxycoumarin (3), and (2'R,3'R,4'S,5'S)-6,8-dimethoxy-7-(3',7'-dimethyl-4',5'-epoxy-2'-hydroxyocta-6'-enyloxy)coumarin (4). Compounds 1-4 strongly enhanced SIRT1 activity in an in vitro SIRT1-NAD/NADH assay and an in vivo SIRT1-p53 luciferase assay. These compounds also increased the NAD-to-NADH ratio in HEK293 cells. The present results suggest that terpenylated coumarins from A. altissima have a direct stimulatory effect on SIRT1 deacetylation activity and may serve as lead molecules for the treatment of some age-related disorders.     

Prenylated flavanones with anti-tyrosinase activity from Dalea boliviana

Three new prenylated flavanones, (2S)-5,7,2'-trihydroxy-5'-(1',1'-dimethylallyl)-8-prenylflavanone (1), (2S)-5,7,2'-trihydroxy-8,3'-diprenylflavanone (2), and (2S)-5,2'-dihydroxy-6',6'-dimethylchromeno-(7,8:2',3')-3'-prenylflavanone (3), and a known chromeno (dimethylpyrano) flavanone, obovatin (4), were isolated from the n-hexane extract of Dalea boliviana roots. The compounds were evaluated in vitro in relation to their inhibitory effect on the tyrosinase activity by using a spectrophotometric method.     

Chemical studies on mexican plants used in traditional medicine, VI. Additional new 4-phenylcoumarins from Exostema caribaeum

Six additional 4-phenylcoumarins have been isolated from the MeOH extract of the bark of Exostema caribaeum. Their structures were determined by physical and chemical methods as 4'-5'-dihydroxy-7-methoxy-4-phenyl-5,2'-oxidocoumarin [1], 5,7,4'-trimethoxy-4-phenylcoumarin [2], 5,3'-dihydroxy-7,4'-dimethoxy-4-phenylcoumarin [3], 5-O-beta-D-galactopyranosyl-7,4'-dimethoxy-4-phenylcoumarin [6], 5-O-beta-D-glucopyranosyl-3',4'-dihydroxy-7-methoxy-4-phenylcoumarin+ ++ [7], and 5-O-(6"-acetyl)-beta-D-galactopyranosyl-3', 4'-dihydroxy-7-methoxy-4-phenylcoumarin [9]. The last four compounds are new natural products.     

Mixed lignan-neolignans from Tarenna attenuata

Six new mixed lignan-neolignans and 20 known compounds were isolated from the whole plant of Tarenna attenuata. By analysis of physical and spectroscopic data, the structures of the new compounds were elucidated as (1R,5R,6R)-6-{4-O-[2-(1-(4-hydroxy-3-methoxyphenyl))glycerol]-3,5-dimethoxyphenyl}-3,7-dioxabicyclo[3.3.0]octan-2-one (1), 5' '-methoxyhedyotisol A (2), 4' '-O-(8-guaiacylglycerol)buddlenol A (3), 5' '-methoxy-4' '-O-(8-guaiacylglycerol)buddlenol A (4), 4,6-dimethoxy-5-hydroxy-3-hydroxymethyl-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrobenzofuran (5), and 7-O-ethylguaiacylglycerol (6). Compounds 1, 5, 6, and 8 showed potent antioxidant activities against H2O2-induced impairment in PC12 cells, and compounds 1, 2, 5, and 7 scavenged DPPH radical strongly with IC50 values of 72, 87, 45, and 55 microM, respectively.     

刺异叶花椒根中香豆素类成分

目的:对刺异叶花椒Zanthoxylum dimorphophyllum var. spinifolum根的化学成分进行研究.方法:采用现代色谱分离技术进行化学成分的分离,运用波谱方法确定结构.结果:从中分离得到5个化合物,分别鉴定为5-甲氧基-7-羟基-6-(3'-甲基-2',3'-二羟基丁基)-香豆素(Ⅰ),6-(3'-甲基-2',3'-二羟基丁基)-7-甲氧基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅱ),6-(3'-甲基-2',3'-二羟基丁基)-7-羟基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅲ),6-(3'-甲基-2',3'-环氧丁基)-7-甲氧基-8-(3″-甲基-丁-2″-烯基)-香豆素(Ⅳ),7-甲氧基-8-(3'-甲基-丁-2'-烯基)-香豆素(Ⅴ).结论:以上化合物均为首次从该植物中分得.     

Potential cncer chemopreventive flavonoids from the stems of Tephrosia toxicaria

A new butenylflavanone, (2S)-5-hydroxy-7-methoxy-8-[(E)-3-oxo-1-butenyl]flavanone (1), and a new rotenoid, 4',5'-dihydro-11,5'-dihydroxy-4'-methoxytephrosin (2), as well as three active flavonoids of previously known structure, isoliquiritigenin (3), genistein (4), and chrysoeriol (5), along with nine known inactive compounds, alpha-toxicarol (6), sumatrol, 6a,12a-dehydro-alpha-toxicarol, 11-hydroxytephrosin, obovatin, marmesin, lupenone, benzyl benzoate, and benzyl trans-cinnamate, were isolated from an ethyl acetate-soluble extract of the stems of Tephrosia toxicaria, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. All isolates were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction. Selected compounds were tested in a mouse mammary organ culture assay to evaluate the inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesions.     

思茅豆腐柴中的黄酮类化学成分研究

 目的研究民族药物思茅豆腐柴(Premna szemaoensis Pei)中的黄酮类化学成分。方法利用Sephadex LH-20及硅胶等色谱技术进行分离纯化,根据理化性质、光谱数据进行结构鉴定。结果得到7个黄酮类化合物,分别鉴定为5,4'-二羟基- 3,7,3'-三甲氧基黄酮(1),5-羟基-3',4',6,7-四甲氧基黄酮(2),5,4'-二羟基-7-甲氧基黄酮醇(3),5,3'-二羟基-7,4'-二甲氧基黄酮醇(4),3',4',5-三羟基-3,7-二甲氧基黄酮(5),5,7-二羟基-4'-甲氧基黄酮(6),5-羟基-7,3',4'-三甲氧基黄酮醇(7)。结论这7个化合物均为首次从思茅豆腐柴中分离得到。     

Antitumor agents. 221.1 buceracidins A and B,two new flavanones from Bucida buceras

As part of a study on antitumor agents from rainforest plants, two new flavanones, buceracidin A (1), 5,2'-dihydroxy-3-methoxy-6,7-(2' ',2' '-dimethylchromene)flavanone, and buceracidin B (2), 5,2'-dihydroxy-6,7-(2' ',2' '-dimethylchromene)flavanone, were isolated together with four known prenylated flavanones, minimiflorin (3), 3-hydroxyminimiflorin (4), 3-methoxyminimiflorin (5), and mundulinol (6), from Bucida buceras. The structures of buceracidins A and B were elucidated from detailed 2D NMR analyses. Among the six flavanones, 3, 5, and 6 were marginally cytotoxic in a human tumor cell line panel.     

Potential cancer chemopreventive constituents of the seeds of Dipteryx odorata (tonka bean)

A new cassane diterpene, dipteryxic acid (1), and a new isoflavonolignan, 5-methoxyxanthocercin A (2), as well as four known active compounds, isoliquiritigenin (3), 6,4'-dihydroxy-3'-methoxyaurone (4), sulfuretin (5), and (+/-)-balanophonin (6), and five known inactive compounds, butin, eriodictyol, 7-hydroxychromone, 7,3'-dihydroxy-8,4'-dimethoxyisoflavone, and (-)-lariciresinol, were isolated from an ethyl acetate-soluble extract of the seeds of Dipteryx odorata, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. Single-crystal X-ray diffraction analysis was used to confirm the relative stereochemistry of compound 1. Selected compounds (3-5) were evaluated in a mouse mammary organ culture assay, with isoliquiritigenin (3) found to exhibit 76% inhibition at a dose of 10 microg/mL.     

穿心莲黄酮类化学成分的研究

目的:研究穿心莲Andrographis paniculata地上部分的黄酮类化学成分。方法:采用硅胶s、ephadex LH-20、反相ODS柱色谱、反相HPLC等从穿心莲85%乙醇提取物中分离得到12个黄酮类化合物,并利用理化性质和波谱学分析手段,鉴定了它们的化学结构。结果:分离并鉴定了12个化合物,分别为5-羟基-7,8-二甲氧基黄酮(1),5-羟基-7,8-二甲氧基二氢黄酮(2),5-羟基-7,8,2′,5′-四甲氧基黄酮(3),2′-甲氧基黄芩新素(4),5-羟基-7,8,2′,3′-四甲氧基黄酮(5),5,4′-二羟基-7,8,2′,3′-四甲氧基黄酮(6),二氢黄芩新素(7),5,7,8-三甲氧基二氢黄酮(8),5,2′-二羟基-7,8-二甲氧基黄酮(9),andrographidine C(10),5,7,4′-三羟基黄酮(11),5,7,3′,4′-四羟基黄酮(12)。结论:化合物6为新天然产物,化合物8,11,12为首次从该属植物中分得。