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).     

Enhanced cytotoxicity in a Z-photoisomer of a benzopyran derivative of propolis

(Z)-2,2-Dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (1) was isolated from Brazilian propolis, together with the known benzopyran derivative, (E)-2, 2-dimethyl-8-(3-methyl-2-butenyl)-benzopyran-6-propenoic acid (2). The structure was determined by spectroscopic analyses, which included 1D and 2D (1)H and (13)C NMR experiments, as well as MS, IR, and UV spectroscopy. Compound 2 rapidly changed to 1 under UV irradiation conditions (365 nm), and the reverse reaction was also observed. The ratio of 1 to 2 reached 2.3 when the reaction began from either 1 or 2, indicating a photostationary state. Compound 1 displayed an approximate 7-fold stronger cytotoxicity against human lung carcinoma cells (HLC-2) compared with 2.     

Three new hyperforin analogues from Hypericum perforatum

Three new analogues of hyperforin (1), pyrano[7,28-b]hyperforin (2), (2R,3R,4S,6R)-6-methoxycarbonyl-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxopropyl)-3-(4-methyl-3-pentenyl)cyclohexanone (3), and (2R,3R,4S,6S)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxopropyl)-3-(4-methyl-3-pentenyl)cyclohexanone (4), were isolated from the aerial parts of Hypericum perforatum (St. John's wort). The structures of 2-4 were elucidated by spectroscopic methods.     

Dibenzyl bromophenols with diverse dimerization patterns from the brown alga Leathesia nana

Six novel dibenzyl bromophenols (1-6) with different dimerization patterns and two propyl bromophenol derivatives (7 and 8), together with 11 known bromophenol derivatives, were isolated from the ethanolic extract of the brown alga Leathesia nana. On the basis of spectroscopic methods the structures of the new compounds were determined as 5,6'-diethyloxymethyl-3,4,2'-tribromo-2,3',4'-trihydroxydiphenyl ether (1), 2-(2,3-dibromo-4,5-dihydroxybenzyl)-3,5-dihydroxy-4-methoxybenzyl alcohol (2), 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (3), 9,10-dihydro-9,10-dimethoxy-3,4,7,8-tetrabromo-1,2,5,6-tetrahydroxyanthracene (4), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (5), rel-(4aS,10aR)-(+/-)-6,7-dibromo-4a-hydroxy-3,8-dihydroxymethyl-10a-methoxy-1,4,4a,10a-tetrahydrodibenzo[b,e][1,4]dioxin-1-one (6), (E)-2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propenal (7), and 2-methyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)-1-propanol (8). Some compounds including 3 showed in vitro selective cytotoxicity against several human cancer cell lines. This is the first brown alga to be reported containing bromophenols.     

New phenylpropenoids, bis(1-phenylethyl)phenols, bisquinolinone alkaloid, and anti-inflammatory constituents from Zanthoxylum integrifoliolum

Five new compounds, including two new phenylpropenoids, (R,E)-1-[4-(3-hydroxyprop-1-enyl)phenoxy]-3-methylbutane-2,3-diol (1) and 4-hydroxy-3-(3-methyl-2-butenyl)cinnamyl alcohol (2), two new bis(1-phenylethyl)phenols, 2,6-bis(1-phenylethyl)phenol (3) and 2,4-bis(1-phenylethyl)phenol (4), and a new bisquinolinone alkaloid, 18-demethylparaensidimerin C (5), together with 17 known compounds have been isolated from the stem wood of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses including extensive 2D nuclear magnetic resonance data. Among the isolates, N-methylflindersine (7), (-)-simulanol (10), and evofolin-C (16) exhibited potent inhibition against N-formylmethionylleucylphenylalanine-induced superoxide production with IC(50) values less than 12 microM.     

Maleimide and maleic anhydride derivatives from the mycelia of Antrodia cinnamomea and their nitric oxide inhibitory activities in macrophages

On cultivation of the fungus Antrodia cinnamomea (BCRC 36799) on a medium, the mycelium was extracted and evaluated for nitric oxide (NO) inhibitory activity. Bioactivity-directed fractionation led to the isolation of two new maleimide derivatives, antrocinnamomins A (1) and B (2), and two new maleic anhydride derivatives, antrocinnamomins C (3) and D (4), along with three known compounds, 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]furan-2,5-dione (5), 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrole-2,5-dione (6), and 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrol-1-ol-2,5-dione (7). Structural elucidation of compounds 1-4 was carried out by spectroscopic data. Compound 1 displayed significant inhibitory effect on nitric oxide (NO) production.     

土贝母中一个新的三萜皂苷

目的对土贝母Bolbostemma paniculatum的三萜皂苷成分进行分离和结构鉴定。方法采用反复柱色谱方法进行分离,通过理化性质和波谱分析鉴定结构。结果从土贝母中分离并鉴定了1个新的三萜皂苷脱木糖土贝母苷丙(dexylosyltubeimoside Ⅲ)。结论化合物为新化合物。     

New naphthopyranone glycosides from Paepalanthus vellozioides and Paepalanthus latipes.

Three new compounds-3, 4-dihydro-10-hydroxy-7-methoxy-3-(R)-methyl-1H-3,4-dihydronaphtho- ]2, 3c]-pyran-1-one-9-O-beta-D-glucopyranoside (1), 3, 4-dihydro-10-hydroxy-7-methoxy-3-(R)-methyl-1H-3,4-dihydronaphtho- [2, 3c]-pyran-1-one-9-O-beta-D-glucopyranosyl-(1-->6)-glucopyranoside (2), and 3,4-dihydro-10-dihydroxy-7-methoxy-3-(R)-methyl-1H-3, 4-dihydronaphtho-[2,3c]-pyran-1-one-9-O-beta-D-allopyranosyl (1-->6)glucopyranoside (3)-were isolated from the leaves of Paepalanthus vellozioides and Paepalanthus latipes and characterized by spectrometric methods, mainly electrospray mass spectrometry and 1D and 2D NMR experiments. These unusual glycosylated dihydronaphthopyranones may serve as taxonomic markers of the genus Paepalanthus, since these compounds were not detected in other genera belonging to the Eriocaulaceae family.     

红葱的化学成分研究

目的研究红葱Eleutherine americana的化学成分。方法采用硅胶柱色谱、Sephadex LH-20柱色谱及重结晶等方法,分离纯化红葱的化学成分,通过MS、NMR等波谱技术确定化合物结构。结果确定了7个化合物的结构,分别为9-hydroxy-8-methoxy-1-methyl-1,3-dihydronaphtho[2,3-c]furan-4-O-β-D-glucopyranoside(1)、eleutherinoside A(2)、豆甾醇-3-O-β-D-葡萄糖苷(3)、kadsuric acid(4)、豆甾醇(5)、1,2-二羟基-8-甲氧基-3-甲基蒽醌(6)、9-methoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyran-5,10-dione(7)。结论化合物1为新化合物,命名为红葱新苷。化合物3～5为首次从该植物中分离得到,化合物6和7为首次获得的新天然产物。     

Two novel cytotoxic benzofuran derivatives from Brazilian propolis

Two novel benzofuran derivatives, propolis-benzofurans A (1) and B (2), were isolated from the MeOH extract of Brazilian propolis, together with two known isoprenylated compounds (E)-3-[2, 3-dihydro-2-(1-methylethenyl)-7-prenyl-5-benzofuranyl]-2-propen oic acid and (E)-3-?4-hydroxy-3-[(E)-4-(2, 3-dihydrocinnamoyloxy)-3-methyl-2-butenyl]-5-prenylphenyl?-2 -propenoi c acid. The structures of these compounds were elucidated on the basis of spectral analysis. Both the new compounds exhibited mild cytotoxicity toward highly liver-metastatic murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells.     

Biosynthesis of the defensive alkaloid (Z)-3-(2-methyl-1-butenyl)pyridine in Stenus similis beetles

Most rove beetles of the genus Stenus protect themselves against microorganisms and predators such as ants and spiders by producing the alkaloid stenusine (1) in their pygidial glands. The biosynthesis of 1 was previously investigated in S. bimaculatus, where L-lysine forms the piperidine ring, L-isoleucine the side chain, and acetate the N-ethyl group. In addition to 1, S. similis keeps the pyridine alkaloid (Z)-3-(2-methyl-1-butenyl)pyridine (2) in its pygidial glands. Feeding S. similis beetles with [D,15N]-labeled amino acids followed by GC/MS analysis showed that L-Lys yields the pyridine ring and L-Ile the 2-methyl-1-butenyl side chain. Thus the alkaloids 1 and 2 probably share two precursor molecules in their biosynthesis.     

Bioactive constituents from Iryanthera megistophylla

Activity-guided fractionation of the 95% ethanol extract from the stem bark of Iryanthera megistophylla led to the isolation of two new compounds, named megislignan [2,3-dimethyl-4-(4-methoxyphenyl)-6-hydroxynaphthalene] (1) and megislactone [(2R,3R,4R)-3-hydroxy-4-methyl-2-(hexacos-17-enyl)butanolide] (2), along with seven known compounds, grandinolide (3), iryantherin K (4), iryantherin L (5), cinchonain I b (6), cinchonain I a (7), procyanidin B-2 (8), and cinchonain IIa (9). The structures of the new compounds were elucidated by spectral data interpretation. Isolates were evaluated for their antibacterial, antifungal, antiviral, and antiacetylcholinesterase activities.     

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).     

小槐花的化学成分研究

目的:系统研究中药小槐花中的化学成分。方法:利用大孔树脂,Sephadex LH-20,ODS及正相硅胶柱等色谱手段进行分离,通过多种波谱学数据分析进行化合物的结构鉴定。结果:从小槐花60%乙醇提取物中分离得到15个化合物,经结构鉴定分别为豆甾醇(1),β-谷甾醇(2),柠檬酚(3),黄槿酮A(4),异柠檬酚(5),kenusanone I(6),neophellamuretin(7),清酒缸酚(8),古柯三醇(9),黄槿酮D(10),山柰酚(11),8-prenylquercetin(12),leachianone G(13),5,7,4’-三羟基-二氢黄酮醇(14),4H-1-benzopyran-4-one,2-(3,4-dihydroxyphenyl)-2,3-dihydro-3,5,7-trihydroxy-8-(3-methyl-2-butenyl)-,(2R-trans)-(9CI)(15)。结论:除化合物8外,所有化合物均为从该种植物中首次分离得到。     

海南粗榧内生真菌S26中次生代谢产物的研究

 目的对海南粗榧内生真菌S26发酵液的化学成分进行研究。方法用多种柱色谱技术对化合物进行分离纯化,用波谱技术和理化性质鉴定化合物的结构,采用MTT法测定化合物的抗肿瘤活性。结果从海南粗榧内生真菌S26的发酵液中分离得到1个环二肽和1个脂肪酸,分别鉴定为(3R,12aS)-3-methyl-2,3,6,7,12,12a-hexahydro-pyrazino[1,2-b]β-carboline-1,4-dione(1)和棕榈酸(2)。结论化合物1是首次分到的天然产物,化合物2在体外对胃癌细胞SGC-7901具有一定的抑制活性。     

6-Alkyl-3,4-dihydro-2H-pyrans: chemical secretion compounds in neotropical harvestmen

The defensive secretions of five neotropical species of harvestmen (Opiliones: Gonyleptidae) from the Brazilian Atlantic Forest were analyzed and chemically characterized by GC-MS and NMR methods. Three of the species, Cobania picea, Roweria virescens, and Serracutisoma proximum, secrete a mixture of 2,3-dimethyl-1,4-benzoquinone and 2-ethyl-3-methyl-1,4-benzoquinone. The secretions produced by the other two species, Iporangaia pustulosa and Neosadocus maximus, contain 1-hepten-3-one, 5-methyl-1-hexen-3-one, and 1-(6-butyl-3,4-dihydro-2H-pyran-2-yl)pentanone (1) as major components, as well as 2,3-dimethyl-1,4-benzoquinone and 2-ethyl-3-methyl-1,4-benzoquinone as minor constituents. The dihydropyran 1-(6-butyl-3,4-dihydro-2H-pyran-2-yl)pentanone (1) is a new natural product, composed of two 1-hepten-3-one subunits formally linked in a hetero-Diels-Alder reaction. The natural product was proven to be racemic, and its biogenetic origin is discussed.     

Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori

The growth-inhibiting activity of Tabebuia impetiginosa Martius ex DC dried inner bark-derived constituents against Helicobacter pylori ATCC 43504 was examined using paper disc diffusion and minimum inhibitory concentration (MIC) bioassays. The activity of the isolated compounds was compared to that of the commercially available anti-Helicobacter pylori agents, amoxicillin, metronidazole, and tetracycline. The biologically active components of Tabebuia impetiginosa dried inner bark (taheebo) were characterized by spectroscopic analysis as 2-(hydroxymethyl)anthraquinone, anthraquinone-2-carboxylic acid, and 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). With the paper disc diffusion assay 2-(hydroxymethyl)anthraquinone exhibited strong activity against Helicobacter pylori ATCC 43504 at 0.01 mg/disc. Anthraquinone-2-carboxylic acid, lapachol and metronidazole were less effective, exhibiting moderate anti-Helicobacter pylori activity at 0.1 mg/disc. Amoxicillin and tetracycline were the most potent compounds tested, displaying very strong activity at 0.005 mg/disc. 2-(Hydroxymethyl)anthraquinone exhibited moderate activity at this dose. Tetracycline still had strong activity at 0.001 mg/disc while amoxicillin had little activity at this dose. In the MIC bioassay, 2-(hydroxymethyl)anthraquinone (2 microg/mL), anthraquinone-2-carboxylic acid (8 microg/mL), and lapachol (4 microg/mL) were more active than metronidazole (32 microg/mL) but less effective than amoxicillin (0.063 microg/mL) and tetracycline (0.5 microg/mL). The anti-Helicobacter pylori activity of seven 1,4-naphthoquinone derivatives (structurally related to lapachol), 1,4-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin), 2-methyl-1,4-naphthoquinone (menadione), 2-hydroxy-1,4-naphthoquinone (lawsone), 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), 5-hydroxy-1,4-naphthoquinone (juglone), and 2,3-dichloro-1,4-naphthoquinone (dichlone) was also evaluated using the paper disc assay. Menadione and plumbagin were the most potent compounds tested with the later still exhibiting very strong activity at 0.001 mg/disc. Menadione, juglone and tetracycline had strong activity at this low dose while the latter two compounds and amoxicillin had very strong activity at 0.005 mg/disc. Lawsone was unusual in that it had very strong activity at 0.1 and 0.05 mg/disc but weak activity at doses of 0.01 mg/disc and lower. Naphthazalin, lapachol and dichlone had similar activities while metronidazole had the lowest activity of all compounds tested. These results may be an indication of at least one of the pharmacological actions of taheebo. The Tabebuia impetiginosa dried inner bark-derived materials, particularly 2-(hydroxymethyl)anthraquinone, merit further study as potential Helicobacter pylori eradicating agents or lead compounds.     

New antioxidant hydroquinone derivatives from the algicolous marine fungus Acremonium sp

A marine fungal isolate, identified as Acremonium sp., was mass cultivated and found to produce two novel hydroquinone derivatives, 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol (1) and 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol-5-beta-D-glucopyranoside (2). Compound 1 and its glucoside 2 possess a most unusual ring system. The new natural products (3R,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)naphthalenone (3) and (3S,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)-naphthalenone (4) were obtained as a 1:0.8 mixture. 2-(1-Methylethylidene)pentanedioic acid (5) was isolated for the first time as a natural product and its structure proven by X-ray analysis. In addition to these compounds an inseparable mixture of three new isomeric compounds, pentanedioic acid 2-(1-methylethylidene)-5-methyl ester (6), pentanedioic acid 2-(1-methylethylidene)-1-methyl ester (7), and pentanedioic acid 2-(1-methylethenyl)-5-methyl ester (8), was also obtained. Isolated together with the new compounds were three known hydroquinone derivatives, 9, 10, and 11. The structures of all compounds were determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, and IR). Each isolate was tested for its antioxidant properties, and compounds 1 and 9-11 were found to have significant activity.     

Pavietin, a coumarin from Aesculus pavia with antifungal activity

A new prenylated coumarin, S-6-[2-(hydroxymethyl)butoxy]-7-hydroxy-4-methyl-2 H-chromen-2-one ( 1), named pavietin, has been isolated from the leaves of an Aesculus pavia genotype along with three known flavonol glycosides, quercetin 3- O-alpha-rhamnoside (quercitrin, 2), quercetin 3- O-alpha-arabinoside ( 3), and isorhamnetin 3- O-alpha-arabinoside (distichin, 4). The chemical structure of compound 1 was determined by chemical and spectroscopic methods, inclusive of UV, MS, and 1D and 2D NMR experiments. It showed appreciable antimicrobial properties against several pathogens, displaying a significant antifungal activity toward one of the main fungal parasites of Aesculus species, Guignardia aesculi. The same biological tests performed with a mixture of flavonoids 2- 4 resulted in weak or no activity. Compound 1 was undetectable in Aesculus hippocastanum, a closely related species lacking resistance to fungal pathogens. The possible role of 1 in plant resistance is discussed.     

New pyranonaphthoquinone and pyranonaphthohydroquinone from the roots of Pentas longiflora

Several quinone type compounds were isolated from the hexane, dichloromethane, and ethyl acetate extracts of the roots of Pentas longiflora. The hexane extract afforded two new compounds, [(3alpha,3'alpha,4beta,4'beta)-3,3']-dimethoxy-cis-[4,4'-bis(3,4,5,10-tetrahydro-1H-naphtho[2,3-c]pyran)]-5,5',10,10'-tetraone (1) and cis-3,4-dihydroxy-3,4-dihydromollugin (2), together with six known compounds, namely, pentalongin, mollugin, trans-3,4-dihydroxy-3,4-dihydromollugin, methyl-2,3-epoxy-3-prenyl-1,4-naphthoquinone-2-carboxylate, tectoquinone, and 3-hydroxymollugin. From the dichloromethane extract were isolated the three known compounds 3-methoxymollugin, methyl-3-prenyl-1,4-naphthoquinone-2-carboxylate, and scopoletin, while the ethyl acetate extract afforded the known 2-methoxy-3-methylanthraquinone.