Cytotoxic 4-phenylcoumarins from the leaves of Marila pluricostata

Bioassay-guided fractionation of the CH(2)Cl(2) extract of the leaves of Marila pluricostata led to the isolation of 17 naturally occurring 4-phenylcoumarins, three of them, 5-hydroxy-8,8-dimethyl-4-phenyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (1), 5-hydroxy-8,8-dimethyl-4-phenyl-6-propionyl-9,10-dihydro-8H-pyrano-[2,3-f]chromen-2-one (2), and 5,7-dihydroxy-8-(3-methylbut-2-enyl)-4-phenylchromen-2-one (3), are new natural compounds; the remaining (4-17) are known mammea-type coumarins. Their structures were established by spectroscopic means. All compounds were tested in cytotoxicity assays against the MCF-7, H-460, and SF-268 human cancer cell lines.     

Benzyl derivatives with in vitro binding affinity for human opioid and cannabinoid receptors from the fungus Eurotium repens

Bioassay-guided fractionation of the fungus Eurotium repens resulted in the isolation of two new benzyl derivatives, (E)-2-(hept-1-enyl)-3-(hydroxymethyl)-5-(3-methylbut-2-enyl)benzene-1,4-diol (1) and (E)-4-(hept-1-enyl)-7-(3-methylbut-2-enyl)-2,3-dihydrobenzofuran-2,5-diol (2), along with seven known compounds (3-9) including five benzaldehyde compounds, flavoglaucin (3), tetrahydroauroglaucin (4), dihydroauroglaucin (5), auroglaucin (6), and 2-(2',3-epoxy-1',3'- heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl)benzaldehyde (7), one diketopiperazine alkaloid, echinulin (8), and 5,7-dihydroxy-4-methylphthalide (9). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data. Compounds 1-4 and 6 showed good binding affinity for human opioid or cannabinoid receptors. These findings have important implications for psychoactive studies with this class of compounds.     

New prenylated anthraquinones and xanthones from Vismia guineensis

From the roots of Vismia guineensis 23 structurally related compounds were isolated and identified. Ten of them are new constituents, namely 3-O-(2-hydroxy-3-methylbut-3-enyl)-emodin (1); 3-O-(2-methoxy-3-methylbut-3-enyl)-emodin (2); 1, 8-dihydroxy-3-(2-methoxy-3-methylbut-3-enyloxy)-6-methylx anthone (3); 1,8-dihydroxy-3-geranyloxy-6-methylxanthone (4); 1, 8-dihydroxy-3-isoprenyloxy-6-methylxanthone (5); 1,8-dihydroxy-3-(3, 7-dimethyl-7-methoxyoct-2-enyloxy)-6-methylxanthone (6); 3-O-(E-3-hydroxymethylbut-2-enyl)-emodin (7); 3-O-(3-hydroxymethyl-4-hydroxybut-2-enyl)-emodin (8); 1, 8-dihydroxy-3-(E-3-hydroxymethylbut-2-enyloxy)-6-methylxa nthone (9); and 1, 8-dihydroxy-3-(3-hydroxymethyl-4-hydroxybut-2-enyloxy)-6- methylxantho ne (10). Their structures were established by means of EIMS and a combination of homonuclear and heteronuclear 2D NMR techniques. Furthermore, an in vitro preliminary screening of antimitotic activity of all the isolated compounds was also evaluated.     

Mycophenolic derivatives from Eupenicillium parvum

A new compound, euparvic acid (1, C(14)H(16)O(6)), and the known compounds 5,7-dihydroxy-4-methylphthalide (2), 6-(3-carboxybutyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (3), 6-(5-carboxy-3-methylpent-2-enyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (4), and 6-(5-carboxy-4-hydroxy-3-methylpent-2-enyl)-7-hydroxy-5-methoxy-4-methylphthalan-1-one (5) were isolated from the EtOAc extract of Eupenicillium parvum. The structure of 1 was determined by interpretation of MS and homo- and heteronuclear 2D NMR spectroscopic data and confirmed by X-ray crystallography. The absolute configuration of 5 was determined via MPA ester derivatization.     

Anti-inflammatory isoflavonoids from the rhizomes of Iris germanica

The anti-inflammatory activity of nine isoflavonoids 5,7-dihydroxy-3-(3'-hydroxy-4',5'dimethoxy)-8-methoxy-4H-1-benzopyran-4-one 1, 5,7-dihydroxy-3-(3'-hydroxyl-4', 5'-dimethoxy)-6-methoxy-4H-1-benzopyran-4-one 2, 5, 7-dihydroxy-3-(4'-hydroxy)-6-methoxy-4H-1-benzopyrane-4-one 3, 5-hydroxy-3-(4'-hydroxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 4, 5-hydroxy-3-(4'-methoxy)-6,7-methylenedioxy-4H-1-benzopyran-4-one 5, 5-methoxy-3-(4'-hydroxy)-6,7-methyenedioxy-4H-1-benzopyran-4-one 6, 5,7-dihydroxy-3-(3'-hydroxy-4'-methoxy)-6-methoxy-4H-1-benzopyran-4-one 7, 5,7-dihydroxy-3-(3'-methoxy-4'-hydroxy)-6-methoxy-4H-1-benzopyran-4-one 8, and isopeonol 9 determined by a spectrophotometric assay using the activated human neutrophils. These isoflavonoids were isolated from an important folkloric medicinal plant Irsa (Iris germanica L.), a member of the family Iridaceae. Structures of these compounds were identified by spectral comparison with the reported data and active members of this group adds into the growing number of non-steroidal anti-inflammatory agents.     

玉竹中的四个高异黄酮

目的：研究玉竹的化学成分。方法：运用各种分离方法（硅胶柱层析,SephadexLH-20）分离化合物,根据理化性质和波谱数据鉴定化合物的结构。结果：从玉竹中分离并鉴定了4个高异黄酮类化合物,结构分别为（±）5,7-dihydroxy-3-（2-hydroxy-4-methoxybenzyl）-6,8-dimethylchroman-4-one（1）,（3R）-5,7-dihydroxy-3-（4-hydroxybenzyl）-6,8-dimethylchroman-4-one（2）,（3R）-5,7-dihydroxy-3-（4-hydroxybenzyl）-8-methoxy-6-methylchroman-4-one（3）,（3R）-5,7-dihy-droxy-3-（4-hydroxybenzyl）-6-methylch-roman-4-one（4）。结论：高异黄酮类化合物在自然界很少见。     

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).     

Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from Erythrina mildbraedii

Inhibition of protein tyrosine phosphatase-1B (PTP1B) has been proposed as a therapy for treatment of type-2 diabetes and obesity. Bioassay-guided fractionation of an EtOAc-soluble extract of the root bark of Erythrina mildbraedii, using an in vitro PTP1B inhibitory assay, resulted in the isolation of three new isoprenylated flavonoids, abyssinone-IV-4'-O-methyl ether (2), 7-hydroxy-4'-methoxy-3'-(3-hydroxy-3-methyl-trans-but-1-enyl)-5'-(3-methylbut-2-enyl)flavanone (3), and abyssinone-VI-4-O-methyl ether (6), along with six known flavonoids, abyssinone-V-4'-O-methyl ether (1), abyssinone-V (4), abyssinone-IV (5), sigmoidin E (7), 4'-hydroxy-5,7-dimethoxyisoflavone (8), and alpinumisoflavone (9). Compounds 1 and 2, 4-7, and 9 inhibited PTP1B activity, with IC50 values ranging from 14.8 +/- 1.1 to 39.7 +/- 2.5 microM. On the basis of the data obtained, flavanones and chalcones with isoprenyl groups may be considered as a new class of PTP1B inhibitors.     

Trypanocidal diarylheptanoids from Aframomum letestuianum

Three new diarylheptanoids, (4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one, letestuianin A (1), (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, letestuianin B (2), and 1,7-bis(4-hydroxyphenyl)heptan-3,5-dione, letestuianin C (3), as well as the known (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one (5) were isolated from Aframomum letestuianum. The known flavonoids 3-acetoxy-5,7,4'-trihydroxyflavanone, 3-acetoxy-7-methoxy-5,4'-dihydroxyflavanone, 7-methoxy-3,5,4'-trihydroxyflavone, and 3,3',4',5,7-pentahydroxyflavan were also obtained from this plant. Their structures were determined using a combination of 1D and 2D NMR techniques. The four diarylheptanoids were tested for growth inhibitory activity in vitro versus bloodstream forms of African trypanosomes. IC(50) values in the range of 1-3 microg/mL were found for compounds 3 and 5.     

绵枣儿中高异黄酮和二苯乙烯类化合物

绵枣儿来源于风信子科植物绵枣儿Scilla scilloides(Lindl.)Druce的鳞茎。本研究采用HPD100大孔树脂、硅胶、Sephadex LH-20、ODS柱色谱和半制备HPLC等方法,从采自河南信阳的绵枣儿中分离出17个化合物;根据化合物的理化性质和波谱数据,分别鉴定为2-羟基-7-甲氧基绵枣儿素(1),绵枣儿素(2),5,7-dihydroxy-3’,4’-dimethoxyspiro{2H-1-benzopyran-7’-bicyclo[4.2.0]octa[1,3,5]-trien}-4-one(3),socialinone(4),4-甲基白藜芦醇(5),(E)-白藜芦醇(6),scillavone A(7),3,9-dihydroeucomnalin(8),3-(3-羟基-4-甲氧基苄基)-5,7-二羟基苯并二氢吡喃-4-酮(9),(3R)-5,7,3’-trihydroxy-4’-methoxyspiro{2H-1-benzopyran-7’-bicyclo[4,2,0]octa[1,3,5]-trien}-4-one(10),scillabene A(11),2-羟基绵枣儿素(12),3-(4-羟基苄基)-5,7-二羟基苯并二氢吡喃-4-酮(13),3-(4-羟基亚苄基)-5,7-二羟基苯并二氢吡喃-4-酮(14),3-(4-羟基苄基)-5-羟基-7,8-二甲氧基苯并二氢吡喃-4-酮(15),3-(4-羟基苄基)-5-羟基-6,7-二甲氧基苯并二氢吡喃-4-酮(16),3-(4-羟基苄基)-5,8-二羟基-7-甲氧基苯并二氢吡喃-4-酮(17),其中化合物3,4,6,9,13和15~17为首次从绵枣儿植物中分离得到。     

Prenylated flavonoid derivatives from the bark of Erythrina addisoniae

Two new prenylated flavanones, 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)licoflavone-4'-methyl ether ( 3) and 2 S-3'-(2-hydroxy-3-methylbut-3-enyl)abyssinone II ( 4), and four known flavanones ( 1, 2, 5, 6) were isolated from the stem bark of Erythrina addisoniae. The structures were elucidated on the basis of their spectroscopic and physicochemical data. None of the compounds showed antioxidative properties. 4'-Methylabyssinone V ( 1) and abyssinoflavanone VII ( 6) showed moderate cytotoxic activity (IC 50 = 5 and 3.5 micromol/L, respectively), but apoptosis (caspase-3/7-activation, nuclear fragmentation) was selectively induced by abyssinoflavanone VII ( 6).     

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.     

A new antifungal metabolite from Penicillium expansum

A new antifungal compound, (3S)-4,6-dihydro-8-methoxy-3,5-dimethyl-6-oxo-3H-2-benzopyran (4), was isolated from Penicillium expansum. During the isolation procedure 4 was determined to be unstable and readily reacted with methanol, ethanol, and water, forming three new isochromans, (1S,3S)-6-hydroxy-1,8-dimethoxy-3,5-dimethylisochroman (1), 1-ethoxy-6-hydroxy-8-methoxy-3,5-dimethylisochroman (2), and 1,6-dihydroxy-8-methoxy-3,5-dimethylisochroman (3), respectively. (3S)-6-Hydroxy-8-methoxy-3,5-dimethylisochroman (5) was reisolated from P. expansum. In fungicide disk assays, compounds 1, 2, and 4 inhibited the mycelial growth of Lasiodiplodia theobromae at 100 microg/mL by 76%, 74%, and 69%, respectively.     

Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease

From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4' "-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl 3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven known compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin, 3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (bisdemethoxycurcumin, 5), 1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6), 1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated following a bioassay-guided fractionation scheme utilizing an assay to detect protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7 were found to more effectively protect PC12 cells from betaA insult (ED(50) = 0.5-10 microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).     

Benzoic acid derivatives from Piper species and their antiparasitic activity

Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively.     

Antihyperglycemic activity and chemical constituents of Eysenhardtia platycarpa

The methanolic extracts from branches (BEP) and leaves (LEP) of Eysenhardtia platycarpa significantly decreased the blood glucose levels in normal and streptozotocin (STZ)-induced diabetic rats. One new flavone, (1"R)-5,4',1"-trihydroxy-6,7-(3",3"-dimethylchroman)flavone (1), together with the known compounds 5,7-dihydroxy-6-methyl-8-prenylflavanone (3), 5,7-dihydroxy-8-methyl-6-prenylflavanone (4), 5,7-dihydroxy-6-prenylflavanone (5), 5,7-dihydroxy-8-prenylflavanone (6), 3-O-acetyloleanolic acid (7), oleanolic acid, 3beta-acetoxy-11alpha,12alpha-epoxy-oleanan-28,13beta-olide, lupeol, betulinic acid, beta-sitosterol, beta-sitosteryl beta-D-glucopyranoside, beta-sitosteryl palmitate, and 3-O-methyl-myo-inositol were isolated from BEP. Additionally, one new flavanone, (2S)-4'-O-methyl-6-methyl-8-prenylnaringenin (2), as well as the known compounds 3, 4, 6, 4'-O-methyl-8-prenylnaringenin (8), and 5-hydroxy-7-methoxy-8-prenylflavanone (9) were isolated from LEP. 3-O-Acetyloleanolic acid (7), identified as the major constituent of BEP, showed a significant decrease (31 mg/kg of body weight, P < 0.05) in the glucose level of STZ-induced diabetic rats. The obtained results correlate with the traditional use of this species.     

Proctoriones A-C: 2-acylcyclohexane-1,3-dione derivatives from peperomia proctorii

The structures of three new compounds isolated from Peperomia proctorii, named proctoriones A-C, have been established by spectroscopic and chemical methods as 2,3-dihydro-5, 8-dihydroxy-2-pentadecyl-4H-benzopyran-4-one (1) and enolic forms of 4-hydroxy-2-octadecanoylcyclohexane-1,3-dione (2) and 4-hydroxy-2-octadec-(11Z)-enoylcyclohexane-1,3-dione (3).     

Cytotoxic constituents of the roots of Ekmanianthe longiflora

Bioactivity-directed fractionation of the CHCl(3) extract of the roots of Ekmanianthe longiflora resulted in the isolation of three new natural products, (2R,3R,4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (1), (2S,3R, 4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (2), and (2R, 3aR,9R,9aR)-9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9 , 9a-hexahydro-naphtho[2,3-b]furan-4-one (3), together with the known compounds 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-quinone (4), 2-acetylnaphtho[2,3-b]furan-4,9-quinone (5), dehydro-iso-alpha-lapachone (6), alpha-lapachone (7), catalponol, and epi-catalponol. The structures of 1-3 were determined using a combination of NMR spectroscopic techniques, and the absolute configurations of compounds 1 and 2 were obtained using Mosher ester methodology. Compounds 4-6 showed significant cytotoxicity in a panel of human cancer cells. alpha-Lapachone (7) exhibited only marginal activity, and catalponol and epi-catalponol were inactive in this regard. When tested at 72 mg/kg/injection in an in vivo mouse P-388 leukemia system, compound 4 was inactive (110% T/C).     

Cytotoxic xanthones from Cudrania tricuspidata

The new isoprenylated tetrahydroxyxanthone, 2,3,6,8-tetrahydroxy-1-(3-methylbut-2-enyl)-5-(2-methylbut-3-en-2-yl)-9H-xanthen-9-one (1), was isolated from the root bark of Cudrania tricuspidata together with macluraxanthone B (2) and cudraxanthone L (3), which were fully characterized by NMR spectroscopic and X-ray crystallographic analyses.     

条叶龙胆药材资源变化及未来发展建议

从本草记载开始阐述了龙胆药材4种基源植物中质量最优的条叶龙胆资源的变化。条叶龙胆野生资源的开发是按由南到北的顺序进行的。我国东北地区条叶龙胆的开发较晚,但由于龙胆的生物学特性及草原破坏等多种原因,在几十年的时间内野生资源便遭到了严重破坏。目前野生资源接近枯竭,栽培严重滞后,致使这一优质龙胆药材市场占有率不断降低。条叶龙胆的可持续发展必须以栽培为主,而育种、栽培技术等与高产密切相关的措施的优化与推广等问题急需解决