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).     

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.     

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.     

Cytotoxic amide alkaloids from Piper boehmeriaefolium

Eight new amide alkaloids (1-8) and 19 known ones were isolated from the whole plant of Piper boehmeriaefolium. Their structures were determined through spectroscopic data analyses. Cytotoxic activity of these amides against human cervical carcinoma HeLa cells was evaluated, and 1-[(9E)-10-(3,4-methylenedioxyphenyl)-9-decenoyl]pyrrolidine (9) exhibited significant inhibitory activity with an IC(50) value of 2.7 μg/mL.     

Bioactive compounds from Peperomia pellucida

Five new compounds (1-5), including two secolignans, two tetrahydrofuran lignans, and one highly methoxylated dihydronaphthalenone, were isolated from the whole plant of Peperomia pellucida. These compounds were accompanied by the known peperomins A, B, C, and E, 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran, 7,8-trans-8,8'-trans-7',8'-cis-7-(5-methoxy-3,4-methylenedioxyphenyl)-7'-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-diacetoxymethyltetrahydrofuran, sesamin, and isoswertisin. New structures were elucidated mainly by NMR and MS techniques, and anticancer activities evaluated in HL-60, MCF-7, and HeLa cell lines. Compound 1 and peperomin E show growth inhibitory effects on the three cancer cell lines with IC(50) values ranging between 1.4 and 9.1 and between 1.8 and 11.1 microM, respectively. Compound 2 has a weak suppressive activity on HL-60 cells (IC(50) = 10.8 microM), while 7,8-trans-8,8'-trans-7',8'-cis-7,7'-bis(5-methoxy-3,4-methylenedioxyphenyl)-8-acetoxymethyl-8'-hydroxymethyltetrahydrofuran exhibits estrogen-like properties (EC(50) = 3.1 microM) in CV-1 cells transfected with human estrogen receptor (ERalpha).     

Prostaglandin inhibitory and antioxidant components of Cistus laurifolius, a Turkish medicinal plant

As Cistus laurifolius has been used traditionally to treat inflammatory and rheumatic disorders, its leaves were tested for prostaglandin (PG) inhibitory and antioxidant activities. The leaf extract showed both activities, i.e., inhibitory effect at 300 microg/ml on PGE1- and E2-induced contractions in guinea pig ileum and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities shown by these dual assays provided sixteen compounds, 1-16. Known compounds 1-12 and 15 were identified as 3-O-methyl quercetin (1), 3,7-O-dimethyl quercetin (2), genkwanin (3), 3,7-O-dimethyl kaempferol (4), 3,4'-O-dimethyl quercetin (5), apigenin (6), 3,4'-O-dimethyl kaempferol (7), ellagic acid (8), beta-sitosterol-3-O-beta-glucoside (9), quercetin 3-O-alpha-rhamnoside (10), 5-O-p-coumaroyl quinic acid methyl ester (11), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-l-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12) and 2,3-dihydro-2-(4'-alpha-l-rhamnopyranosyloxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5-benzofuranpropanol (15). New lignan glycosides 13 and 14 were determined to be olivil 9-O-beta-D-xyloside and berchemol 9-O-rhamnoside, respectively. Compound 16 was isolated as a 2:1 mixture of two diastereomers, the major one of which was determined to be (7S,8R)-dihydrodehydrodiconiferyl alcohol 9'-O-alpha-L-rhamnoside. The structures were determined by detailed 2D NMR analysis together with NOEDF and CD. PG inhibitory effect was observed in 1, 5, 10, 12 and 16 at 30 microg/ml and antioxidant activity, in 1, 2, 8, 10, 12-14 and 16.     

Phenolic compounds from the roots of Jordanian viper's grass, Scorzonera judaica

Nine new phenolic compounds, 3S-hydrangenol 40-O-R-L-rhamnopyranoysl-(1-->3)-β-D-glucopyranoside (1), thunberginol F 7-O-β-D-glucopyranoside (2), 2-hydroxy-6-[2-(4-hydroxyphenyl)-2-oxo-ethyl]benzoic acid (3), 2-hydroxy-6-[2-(3,4-dihydroxyphenyl)-2-oxo-ethyl]benzoic acid (4), 2-hydroxy-6-[2-(3,4-dihydroxyphenyl-5-methoxy)-2-oxoethyl]benzoic acid (5), hydrangeic acid 40-O-β-D-glucopyranoside (6), E-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)dihydrofuran-2-one (7), Z-3-(3,4-dihydroxybenzylidene)-5-(3,4-dihydroxyphenyl)-2(3H)-furanone (8), and 4-[β-D-glucopyranosyl)hydroxy]-pinoresinol (9), and nine known compounds were isolated from the roots of Scorzonera judaica. Structures of 1-9 were elucidated by mass spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy.All compounds were evaluated for cytotoxic activity.     

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.     

Pseudotrienic acids A and B, two bioactive metabolites from Pseudomonas sp. MF381-IODS

Bioassay-guided fractionation of the liquid culture broth of Pseudomonas sp. MF381-IODS yielded two new antimicrobial substances, identified as (2E,4E,6E)-9-[((2S,3R)-3-hydroxy-4-{[(3E,5E,7RS)-7-hydroxy-4-methylhexadeca-3,5-dienoyl]amino}-2-methylbutanoyl)amino]nona-2,4,6-trienoic acid and the tetradeca equivalent, named pseudotrienic acids A (1) and B (2), respectively. The compounds are prone to lactone formation, and their structures suggest them to be derived from ring opening of a macrolide. Pseudotrienic acids A and B inhibited growth of Staphylococcus aureus (MIC 70 microg/mL) and Pseudomonas syringae pv. syringae (MIC 70 microg/mL). Two known antimicrobial compounds, the polyketide 2,3-deepoxy-2,3-didehydrorhizoxin (3) and the tryptophan-derived pyrrolnitrin (4), were also identified.     

New antimycobacterial and antimalarial 8,9-secokaurane diterpenes from Croton kongensis

Two new 8,9-secokaurane diterpenes, ent-8,9-seco-7alpha,11beta-diacetoxykaura-8(14),16-dien-9,15-dione (1) and ent-8,9-seco-8,14-epoxy-7alpha-hydroxy-11beta-acetoxy-16-kauren-9,15-dione (2), together with two known compounds, ent-8,9-seco-7alpha-hydroxy-11beta-acetoxykaura-8(14),16-dien-9,15-dione (3) and ent-7beta-hydroxy-15-oxokaur-16-en-18-yl acetate, were isolated from Croton kongensis. This is the first report on the presence of 8,9-secokauranes in the plant genus Croton. Diterpenes 1-3 exhibited antimycobacterial activity with minimum inhibitory concentrations (MICs) of 25.0, 6.25, and 6.25 microg/mL, respectively, and possessed antimalarial activity with IC(50) ranges of 1.0-2.8 microg/mL. They also demonstrated comparable cytotoxicity toward the Vero (IC(50) ranged from 0.9 to 3.2 microg/mL), KB (IC(50) from 1.2 to 13.8 microg/mL), and BC cell lines (IC(50) from 1.1 to 2.2 microg/mL, except for compound 1, which was inactive against BC cells).     

桫椤化学成分研究

目的:研究桫椤Cyathea spinulosa Wall.的化学成分。方法:采用各种柱色谱进行分离纯化,根据理化性质和光谱数据进行结构鉴定。结果:从桫椤的乙醇提取物中共分离鉴定了8个化合物,分别为:豆甾-4-烯-3,6-二酮(1)、豆甾-3,6-二酮(2)、麦角甾醇(3)、原儿茶醛(4)、1-O-β-D-glucopyranosyl-(2S,3R,4E,8Z)-2-[(2-hydroxyoctade-canoyl)amido]-4,8-octadecadiene-1,3-diol(5)、(2S,3S,4R)-2-[(2'R)-2'-hydroxytetracosanoylamino]-1,3,4-octade-canetriol(6)、β-谷甾醇(7)、胡萝卜苷(8)。结论:其中,化合物1～6为首次从该植物中分离得到。     

刺五加的化学成分研究

目的研究五加科五加属植物刺五加Acanthopanax senticosus的化学成分。方法利用各种色谱技术进行分离,根据光谱数据鉴定结构。结果从刺五加中分离得到12个已知成分,分别鉴定为刺五加酮(1)、刺五加苷B1(2)、4-羟基-2-甲氧基苯基-1-O-β-D-葡萄糖苷(3)、alimoxide(4)、赤式-1-(4-羟基-3-甲氧基苯基)-2-{4-[(E)-3-羟基-1-丙烯基]-2-甲氧基苯氧基}-1,3-丙二醇(5)、erythro-1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(6)、tortoside A(7)、表丁香脂素4′-O-β-D-葡萄糖苷(8)、(+)-lyoniresinol(9)、苯甲基-O-α-L-鼠李吡喃糖基(1→6)-β-D-葡萄吡喃糖苷(10)、2,6-二甲氧基-4-(3-羟基丙烯基)苯基-1-O-α-L-鼠李吡喃糖基-(1→6)-β-D-葡萄吡喃糖苷(11)、β-氨甲酰基吡啶(12)。结论化合物3～5、10～12为首次从该植物中分离得到。     

beta-triketones from myrtaceae: isoleptospermone from leptospermum scoparium and papuanone from corymbia dallachiana

Naturally occurring beta-triketones, isoleptospermone [3, 5-hydroxy-4-(2-methyl-1-oxopentyl)-2,2,6, 6-tetramethyl-4-cyclohexene-1,3-dione) from Leptospermum scoparium] and papuanone [6, 5-hydroxy-4-(1-oxohexyl)-2,2,6, 6-tetramethyl-4-cyclohexene-1,3-dione from Corymbia dallachiana], have been synthesized. Full spectral data are reported for the first time. The 13C NMR spectra of 3, 6, and the other triketones flavesone (2), leptospermone (4), and grandiflorone (5) found in Myrtaceous plants are fully assigned.     

小黄皮茎的化学成分及生物活性研究

目的研究小黄皮Clausenaemarginata茎的化学成分及其保肝活性。方法采用硅藻土、硅胶等多种柱色谱、中压制备液相色谱(MPLC)及制备型HPLC等方法对小黄皮茎的化学成分进行分离纯化,根据化合物理化性质结合现代波谱学方法鉴定化合物结构;并测试其对DL-半乳糖胺诱导肝细胞损伤的保护活性及其对脂多糖(LPS)诱导小鼠小胶质BV2细胞产生一氧化氮(NO)的抑制活性。结果从小黄皮茎的95%乙醇提取物的氯仿部位分离得到11个化合物,分别鉴定为nordentatin(1)、oxanordentatin(2)、5′-羟基葡萄内酯(3)、7-[(E)-7′-羟基-3′,7′-二甲基-2′,5′-二烯]-香豆素(4)、7-羟基香豆素(5)、claulamine A(6)、γ-崖椒碱(7)、开环异落叶松脂素(8)、2-{4-[(1E)-3-hydroxyprop-1-en-1-yl]-2,6-dimethoxyphenoxy}propane-1,3-diol(9)、2-[4-(3-hydroxy-1-propenyl)-2-methoxyphenoxy]-1,3-propanediol(10)、甲基-2-O-β-D-吡喃葡萄糖基苯甲酸(11)。其中,化合物1~5为香豆素类化合物,6为咔唑生物碱,7为呋喃喹啉类生物碱,8为木脂素类化合物,9、10为苯丙素类化合物,11为酚酸类化合物。结论化合物2~4、7~11为首次从该植物中分离得到,化合物5和7对DL-半乳糖胺诱导的肝细胞损伤具有一定的保护活性,化合物11对LPS诱导BV2细胞产生NO具有一定的抑制作用。     

Zyzzyanones B-D, dipyrroloquinones from the marine sponge Zyzzya fuliginosa

Zyzzyanones B, C, and D (2-4), three new dipyrroloquinones with a pyrrolo[3,2-f]indole-4,8(1H,7H)-dione skeleton, have been isolated from the Australian marine sponge Zyzzya fuliginosa. The known zyzzyanone A, makaluvamines C, E, G, H, and L, damirones A and B, 3,7-dimethylguanine, and 4-hydroxybenzoic acid were also isolated. The structures of the new compounds 2-4 were established by extensive NMR spectroscopic data. Compounds 2-4 showed moderate cytotoxic activity against mouse Ehrlich carcinoma cells (IC50 25 microg/mL).     

Allergy-preventive phenolic glycosides from Populus sieboldii

Allergy-preventive activity was demonstrated for an extract of the bark of Populus sieboldii in a continuing search for allergy-preventive substances from natural sources. By bioassay-directed fractionation of this plant bark, two new phenolic glycosides, siebolside A {2-hydroxy-5-[(benzoyloxy)methyl]phenyl (6'-O-acetyl) beta-D-glucopyranoside} (1) and siebolside B {2-hydroxy-5-[(benzoyloxy)methyl]phenyl beta-D-glucopyranoside} (2), were isolated, together with three known compounds, salicin (3), sakuranin (4), and neosakuranin (5). The structures of 1 and 2 were elucidated by spectroscopic methods. Compounds 1-5 all showed allergy-preventive effects.     

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.     

The antimycobacterial constituents of dill (Anethum graveolens)

As part of a project to characterize selected members of the Kuwaiti flora for their phytochemistry and antimycobacterial activity, a new furanocoumarin, 5-[4'-hydroxy-3'-methyl-2'-butenyloxy]-6,7-furocoumarin (3), was isolated from the whole herb of Anethum graveolens. The known compounds oxypeucedanin (1), oxypeucedanin hydrate (2) and falcarindiol (4) were also isolated from this plant. The structure of each compound was determined by interpretation of NMR and mass spectrometric data. The three known compounds exhibited antibacterial activity against a panel of rapidly growing mycobacteria with minimum inhibitory concentration (MIC) values in the range 2-128 microg/mL.     

Cytotoxic flavonoids from Platymiscium floribundum

Two new isoflavonoids, 7-hydroxy-6,4'-dimethoxy-isoflavonequinone (1) and 2'-hydroxy-6,4',6' ',4' '-tetramethoxy-[7-O-7' ']-bisisoflavone (2), and seven other known flavonoids, 3-hydroxy-9-methoxypterocarpan (medicarpin), 3,10-dihydroxy-9-methoxypterocarpan, 3,9-dimethoxypterocarpan (homopterocarpin) (3), 2,3,9-trimethoxypterocarpan (4), 3,4-dihydroxy-9-methoxypterocarpan (vesticarpan) (5), 2',4,4'-trihydroxychalcone (isoliquiritigenin), and 7,4'-dihydroxyflavanone (liquiritigenin) (6), were isolated from the heartwood of Platymiscium floribundum. The structures of compounds 1 and 2 were established by spectroscopic methods. Compounds 3-6 showed cytotoxic activity when evaluated against five human cancer cell lines in vitro.     

石南藤化学成分研究

目的:对石南藤的化学成分进行研究。方法:利用正相硅胶、反相硅胶和葡聚糖凝胶Sephadex LH-20等多种柱色谱技术对石南藤的化学成分进行分离,根据核磁共振光谱等数据进行结构鉴定,对分离得到的化合物进行DPPH自由基清除活性和乙酰胆碱酯酶抑制活性检测。结果:从石南藤乙酸乙酯相分离鉴定了10个化合物,分别为:3,4-亚甲二氧基-苯甲酸(1)、香草酸(2)、苯甲酸(3)、N-p-香豆酰酪胺(4)、风藤酮(5)、风藤奎醇(6)、异风藤奎醇A(7)4、-羟基-3,5-二甲氧基-苯甲酸(8)、风藤酰胺(9)和二氢荜茇明宁碱(10)。结论:化合物1～6为首次从石南藤中分离得到,化合物28、具有一定的自由基清除活性,其EC50值分别为224.33μg/mL和11.44μg/mL,化合物1～10均无乙酰胆碱酯酶抑制活性。