Isolation of substances with antiproliferative and apoptosis-inducing activities against leukemia cells from the leaves of Zanthoxylum ailanthoides Sieb. & Zucc

Extraction of the leaves of Zanthoxylum ailanthoides Sieb. & Zucc. affords extracts and four isolated compounds which exhibit activities against leukemia cells. The chloroform-soluble fraction (ZAC) of the crude extract of this plant showed cytotoxic activity against human promyelocytic leukemia (HL-60) and myelomonocytic leukemia (WEHI-3) cells with IC₅₀ values of 73.06 and 42.22 μg/mL, respectively. The active ZAC was further separated to yield pheophorbide-a methyl ester (1), pheophorbide-b methyl ester (2), 13²-hydroxyl (13²-S) pheophorbide-a methyl ester (3) and 13²-hydroxyl (13²-R) pheophorbide-b methyl ester (4) whose structures were confirmed by spectroscopic methods. Compounds 2-4 showed cytotoxic activities against both leukemia cells with IC₅₀ value in the range of 46.76-79.43 nM, whereas compound 1 exhibited only weak cytotoxic activity. The extracts and compounds 1-4 also induced apoptosis and DNA damage in leukemia cells after treatment. The results suggested that the Z. ailanthoides is biologically active against leukemia cells.     

Antitumor agents. Part 209: Pheophorbide-a derivatives as photo-Independent cytotoxic agents

A methanolic crude extract of the plant Garuga pinnata Roxb. (Burseraceae) showed promising cytotoxic activity against a panel of human tumor cell lines in vitro, including KB and its drug-resistant sublines (Ferguson et al. Cancer Res. 1988, 48, 5956). Pheophorbide-a and-b methyl esters (3,4) were isolated as active principles with broad photo-dependent cytotoxic activities in the micromolar range. These findings prompted SAR studies of known and novel pheophorbide-a derivatives as photo-dependent and photo-independent cytotoxic agents. The results showed that zinc-protoporphyrin IX (10), zinc 13(R)-hydroxypheophorbide-a methyl ester (22), and zinc chlorin-e6 trimethyl ester (13) possessed photo-independent cytotoxic activity. Compounds 13 and 22 were the most active cytotoxic agents of the series (mean ED(50) 4.6 +/- 1.0 microM and 5.7 +/- 0.7 microM, respectively) against KB cells incubated in the dark.     

Free radical oxidation of 15-(S)-hydroxyeicosatetraenoic acid with the Fenton reagent: characterization of an epoxy-alcohol and cytotoxic 4-hydroxy-2E-nonenal from the heptatrienyl radical pathway

The oxidation of (5Z,8Z,11Z,13E,15S)-15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-(S)-HETE, 1a) with the Fenton reagent (Fe2+/EDTA/H2O2) was investigated. In phosphate buffer, pH 7.4, the reaction proceeded with 75% substrate consumption after 1 h to give a mixture of products, one of which was identified as (2E,4S)-4-hydroxy-2-nonenal (3a, 18% yield). Methylation of the mixture with diazomethane allowed isolation of another main product which could be identified as methyl (5Z,8Z,13E)-11,12-trans-epoxy-15-hydroxy-5,8,13-eicosatrienoate (2a methyl ester, 8% yield). A similar oxidation carried out on (15-(2)H)-15-HETE (1b) indicated complete retention of the label in 2b methyl ester and 3b, consistent with an oxidation pathway involving as the primary event H-atom abstraction at C-10. Overall, these results support the recently proposed role of 1a as a potential precursor of the cytotoxic gamma-hydroxyalkenal 3a and disclose a hitherto unrecognized interconnection between 1a and the epoxy-alcohol 2a, previously implicated only in the metabolic transformations of the 15-hydroperoxy derivative of arachidonic acid.     

Free radical oxidation of coriolic acid (13-(S)-hydroxy-9Z,11E-octadecadienoic acid)

The reaction of (13S,9Z,11E)-13-hydroxy-9,11-octadecadienoic acid (1a), one of the major peroxidation products of linoleic acid and an important physiological mediator, with the Fenton reagent (Fe(2+)/EDTA/H(2)O(2)) was investigated. In phosphate buffer, pH 7.4, the reaction proceeded with >80% substrate consumption after 4h to give a defined pattern of products, the major of which were isolated as methyl esters and were subjected to complete spectral characterization. The less polar product was identified as (9Z,11E)-13-oxo-9,11-octadecadienoate (2) methyl ester (40% yield). Based on 2D NMR analysis the other two major products were formulated as (11E)-9,10-epoxy-13-hydroxy-11-octadecenoate (3) methyl ester (15% yield) and (10E)-9-hydroxy-13-oxo-10-octadecenoate (4) methyl ester (10% yield). Mechanistic experiments, including deuterium labeling, were consistent with a free radical oxidation pathway involving as the primary event H-atom abstraction at C-13, as inferred from loss of the original S configuration in the reaction products. Overall, these results provide the first insight into the products formed by oxidation of 1a with the Fenton reagent, and hint at novel formation pathways of the hydroxyepoxide 3 and hydroxyketone 4 of potential (patho)physiological relevance in settings of oxidative stress.     

丽江蚤缀的化学成分

利用DiaionHP20及硅胶柱层析进行化合物的分离,从乙酸乙酯萃取部位分离得到了8个化合物,借助多种光谱技术进行结构鉴定分别鉴定为E对甲氧基肉桂酸(pEMethoxycinnamicacid)(Ⅰ),Z对甲氧基肉桂酸甲酯(3(4Methoxyphenyl)2Zpropenoicacidmethylester)(Ⅱ),Z对甲氧基肉桂酸(pZMethoxycinnamicacid)(Ⅲ),E对羟基肉桂酸甲酯(pEHedroxycinnamicacidmethylester)(Ⅳ),2,4,6,4′fourhydroxydihydrochalcone(Ⅴ),5,7,4′三羟基3′,5′二甲氧基黄酮(Ⅵ),β谷甾醇(βSidosterol)(Ⅶ),胡萝卜苷(Daucosterol)(Ⅷ)。所有化合物均为已知化合物,并首次从该植物中分得。     

Circadian rhythm of anti-fungal prenylated chromene in leaves of Piper aduncum

Leaves of Piper aduncum accumulate the anti-fungal chromenes methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl-2'-butenyl)-2H-1-chromene-6-carboxylate (2). The enzymatic formation of 2 from dimethylallyl diphosphate and 1 was investigated using cell-free extracts of the title plant. An HPLC assay for the prenylation reaction was developed and the enzyme activity measured in the protein extracts. The prenyltransferase that catalyses the transfer of the dimethylallyl group to C-2' of 1 was soluble and required dimethylallyl diphosphate as the prenyl donor. In the leaves, the biosynthesis of the prenylated chromene 2 was time-regulated and prenyltransferase activity depended upon circadian variation. Preliminary characterisation and purification experiments on the prenyltransferase from P. aduncum have been performed.     

Stereospecificity of the hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids produced by cultured bovine endothelial cells

Characterization of the stereospecificity of the derivatives of arachidonic acid and linoleic acid produced by endothelial cells is needed to define the enzymatic origin of these compounds and their role in vascular physiology. In studies utilizing two bovine endothelial cell lines (CPAE and AG04762), both free 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-hydroxyeicosatetraenoic acid (11-HETE) were generated during incubations with exogenous arachidonic acid and both free 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were generated during incubations with exogenous linoleic acid. Esterification of 15-HETE, 9-HODE and 13-HODE during these incubations was demonstrated. The analyses included reversed-phase high performance liquid chromatography of the free acid and its methyl ester and chiral separation of the methyl ester on straight phase chiral columns. The ratio of 9-HODE/13-HODE averaged 2.7 in the chromatographic analyses of the extracts of the incubations with linoleic acid. The combined production of 13-HODE and 9-HODE from linoleic acid was four times greater than that of 15-HETE and 11-HETE from arachidonic acid. With regard to the products of the CPAE endothelial cell line, the S/R ratio of the stereoisomers averaged 1.5 for free 15-HETE, 5.7 for free 13-HODE and 0.2 for free 9-HODE. The 11-HETE had strict (R) stereospecificity. The products from the AG04762 endothelial cell line had similar stereochemistry. All these stereochemical findings point to the activity of a cyclooxygenase rather than that of a lipoxygenase.     

Sesquiterpenoids from roots of Taraxacum laevigatum and Taraxacum disseminatum

Chromatographic separation of ethanolic root extracts of Taraxacum laevigatum and Taraxacum disseminatum afforded a total of eight germacrane- and eudesmane-type sesquiterpenoids. including new compounds, 1beta,3beta,6alpha-trihydroxy-4alpha( 15)-dihydrocostic acid methyl ester and its 1-O-beta-glucopyranoside. Their structures were established by spectroscopic analyses. In addition, the structure of 4alpha(15), 11beta(13)-tetrahydroridentin B-1-O-beta-glucopyranoside was elucidated by extensive NMR studies.     

Diterpenoids from Calceolaria inamoena

Four 9-epi-ent-labdanes were isolated from the aerial parts of Calceolaria inamoena. Their structures, 2beta-hydroxy-9-epi-ent-labda8(17)-13(E)dien-15-oic acid, 2beta-hydroxy-9-epi-ent-labda8(17)-13(Z)dien-15-oic acid, 2beta-hydroxy-9-epi-ent-labda8(17)-13(E)dien-15-al and 2beta-hydroxy-9-epi-ent-labda-8(17)-13(Z)dien-15-al, were established by spectroscopic methods including by analysis of 2 dimensional heteronuclear correlation experiments 1H/13C (normal and long range), and NOE and gs-sel-1D-NOESY and TOCSY of their methyl ester or acetyl derivatives.     

Isolation and identification of potential cancer chemopreventive agents from methanolic extracts of green onion (Allium cepa)

Phase II xenobiotic metabolizing enzymes confer amelioration of risk arising from potentially carcinogenic chemicals derived both endogenously, and exogenously, from food and the environment. In this study, efforts were made to isolate and identify potentially cancer preventive constituents from methanolic extracts of green onion (Allium cepa) directed by the quinone reductase (QR) induction bioassay using murine hepatoma (Hepa 1c1c7) cells. Crude methanolic extracts of green onion tissue were solvent-partitioned, and subsequently fractionated by flash chromatography, thin layer chromatography and high pressure preparative liquid chromatography to afford pure QR-inducing isolates. Multiple isolates were found active at inducing QR. One newly identified compound, 5-hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one (3), and four known compounds: 5-(hydroxymethyl) furfural (1), acetovanillone (2), methyl 4-hydroxyl cinnamate (4) and ferulic acid methyl ester (5), were isolated and identified as active agents.     

水麻的化学成分研究(英文)

从水麻(Debregeasia orientalis C J Chen)地上部分的95%乙醇提取物中首次分离到18个化合物,应用波谱方法或与已知品对照的手段鉴定它们为棕榈酸 (1)、正二十烷酸 (2)、正二十烷酸甲酯 (3)、β-谷甾醇 (4)、Monogynol A (5)、白桦酸 (6)、Hederagenin (7)、β-胡萝卜甙 (8)、18αH-20(29)-烯-3-酮-乌苏烷 (9)、3,4-开环-20(29)-烯-乌苏烷-3-酸 (10)、Pomolic acid (11)、表儿茶素 (12)、儿茶素 (13)、槲皮素 (14)、槲皮素-3-O-β-D-吡喃葡萄糖苷 (15)、紫丁香苷 (16)、紫丁香酚苷 (17)和山萘酚-3-O-β-D-芦丁糖苷 (18).     

傣药“雅糯妙”（肾茶）正丁醇部位的化学成分研究

目的：对肾茶正丁醇部位进行系统分离和化合物鉴定,为探索肾茶药理活性物质基础研究奠定基础;方法：采用多种分离纯化技术（硅胶柱层析色谱、反相硅胶柱色谱、SephadesLH-20、半制备型高效液相色谱等）对肾茶正丁醇部位化学成分进行系统的分离纯化,得到单体化合物;运用电喷雾质谱（ESI—MS）、核磁共振氢谱（1HNMR）、核磁共振碳谱（13CNMR／DEPT）和二维核磁共振谱（HSQC,HMBC）对所得单体化合物进行结构鉴定。结果：从肾茶正丁醇部位中共分离得到9个化合物,分别鉴定为：原儿茶酸甲酯（1）、原儿茶醛（2）、原儿茶酸（3）、3,4．二羟基苯乙酸甲酯（4）、3,4一二甲氧基乙酸甲酯（5）、2,5-二羟基苯甲醛（6）、苯甲酸（7）、咖啡酸（8）、迷迭香酸（9）。结论：肾茶正丁醇部位主要化学成分为酚醛、芳香酸及其衍生物,除分离得到之前献报告的咖啡酸、迷迭香酸等外,还首次分离鉴定4个化合物（1,4,5,6）,其中化合物6为首次从植物中分离得到,并首次对该化合物核磁数据进行了归属;化合物1、4、5均为首次从肾荼属植物中分离得到。     

ACAT inhibition of alkamides identified in the fruits of Piper nigrum

In this study, via a bioactivity-guided fractionation of MeOH extracts of the fruits of Piper nigrum, alkamide (5) and five previously-identified alkamides were isolated. Their structures were elucidated via spectroscopic analysis ((1)H, (13)C NMR and ESI-MS), as follows: retrofractamide A (1), pipercide (2), piperchabamide D (3), pellitorin (4), dehydroretrofractamide C (5) and dehydropipernonaline (6). The IC(50) values determined for the compounds were 24.5 (1), 3.7 (2), 13.5 (3), 40.5 (4), 60 (5) and 90 microM (6), according to the results of an ACAT enzyme assay system using rat liver microsomes. These compounds all inhibited cholesterol esterification in HepG2 cells.     

Phenolic acid amides: a new type of DNA strand scission agent from Piper caninum

In a survey of the active components of crude plant extracts for their ability to cleave DNA, a crude extract prepared from Piper caninum was found to induce the relaxation of supercoiled pBR322 plasmid DNA in the presence of Cu(2+). Bioassay-guided fractionation was carried out on this extract, guided by an in vitro DNA strand scission assay. Three active principles were isolated and identified as N-cis-feruloyl tyramine (1),N-trans-feruloyl tyramine (2), and 1-cinnamoylpyrrolidine (3). Compounds 1-3 represent a structurally new type of DNA strand scission agent.     

Studies on the Constituents of Aristolochia versicolar S. M. Hwang

Twenty-four constituents were isolated from the root of Aristolochia versicolar S. M. Hwang (collected from Guangxi province, China). Ten of them (two novel sesquiterpene lacrones and eight known compounds) were reported recently. This paper deals with the other eight compounds. From the petroleum ether extraction a sesquiterpene lactone, C15H20O2, mp. 94–95℃ [α]D36 –49˚ (C=1.8, EtOH), confirmed to be isoaristolactone, was obtained from plants for the first time. On the basis of spectral analysis (UV, IR, 1HNMR, 13CNMR, MS) and chemical reactions its structure was determined as B2. From the petroleum enter unsoluble sec- tion 6-methoxyaristolic acid methyl ester (D1), aristolic acid (D3), 6-methoxyaristolic acid (ari- stolinic acid) (D4f), 6-methoxyaristolochic acid methyl ester (D4y), aristolochic acid A(D5), β-sitosterol-D-glucoside (D10) and allantoin (C2) were isolated and identified. Dx, Ds, and Ds show ed antifertility activity in mice.     

Prenylated benzoic acid derivatives from Piper aduncum L. and P. hostmannianum C. DC. (Piperaceae)

The bioactivity-guided fractionation of the crude extracts from leaves of Brazilian species Piper aduncum and Piper hostmannianum by means of bioautography using the fungi Cladosporium cladosporioides and C. sphaerospermum afforded prenylated methyl benzoate, chromenes, and dihydrobenzopyran derivatives as antifungal compounds. The isolation and structural elucidation of a new compound methyl 4-hydroxy-3-(2′-hydroperoxy-3′-methyl-3′-butenyl)benzoate were performed by application of chromatographic techniques and spectroscopic analyses.     

石菖蒲的化学成分研究

运用色谱法从石菖蒲根茎提取物中分离得到18个化合物,经波谱学分析鉴定为:(7S,8R)-4,9’-di-hydroxyl-3,3’-dimethoxyl-7,8-dihydrobenzofuran-1’-propylneolignan(1),(7S,8R)-4,9’-dihydroxyl-3,3’-dimethoxyl-7,8-dihydrobenzofuran-1’-propylneoligan-9-O-β-D-glucopyranoside(2),7’-hydroxylariciresinol-9-acetate(3),5-羟基-3,7,4’-三甲氧基黄酮(4),野漆树苷(5),紫云英苷(6),松属素-3-O-芸香糖苷(7),山奈酚-3-O-芸香糖苷(8),德钦红景天苷(9),isoschaftoside(10),5-羟甲基糠醛(11),反式桂皮酸(12),3,7-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oicacid(13),3,7-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester(14),环阿屯醇(15),胡萝卜苷(16),羽扇豆醇(17),(22E,24R)-ergosta-5,7,22-trien-3β-ol(18)。除化合物4、11和16外,其余15个化合物均为首次从该植物中分离得到。     

Effects of (15S)-15-methyl prostaglandin F2 methyl ester and estrogens upon the corpus luteum and conceptus of the rhesus monkey

The corpus luteum inhibiting properties of eighteen 15-methyl prostaglandin analogs were determined in the rhesus monkey during concomitant stimulation of the corpus luteum with chorionic gonadotropin. The methyl ester of (15S)-15-methyl PGF_2^α (15M-PGF_2^α, 12.5 mg/monkey) lowered serum progesterone to 12% of pretreatment values within 24 hours, however progesterone returned to normal limits within 48 hours. Elongation of the top side-chain by two carbons (2a,2b-dihomo-15M-PGF_2^α methyl ester, 13 mg/monkey), substitution of a hydroxymethyl group at carbon 1 (2-decarboxy-2-hydroxymethyl-15M-PGF_2^α, 12 mg/monkey), or the formation of the carbon 1 amide (15M-PGF_2^α amide, 12.5 mg/monkey) improved the inhibitory activity of 15M-PGF_2^α; serum progesterone for these 3 analogs was depressed to 15–30% of pretreatment levels within 24 hours, and did not return to control values. Luteal function was not inhibited (12 or more mg/monkey) when the 15-methyl group was placed in the R configuration, the top side chain was shortened by two carbons, an amino group was substituted for carbon 1, the 5-oxa modification was added, or the 1,9-lactone was formed. Some other modifications of 15M-PGF_2^α were also inactive, although not all were tested at equivalent doses: 2,2-difluoro; 4,5-cis-didehydro; 9,11-dideoxy-9α,11α-dichloro; 11-deoxy; 17-phenyl; 1,15-lactone; and the p-benzamidophenyl ester of 2a,2b-dihomo-15M-PGF_2^α. (15S)-15-Methyl PGE₂ methyl ester (1 mg/monkey) depressed serum progesterone concentrations to 42% of pretreatment values within 24 hours; 2a,2b-dihomo-11-deoxy-(15S)-15-methyl PGE₂ methyl ester was inactive (5 mg/monkey). A corpus luteum inhibiting action of certain 15-methyl prostaglandins can be demonstrated in the rhesus monkey.     

Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp. and Siphonochalina spp. sponges.

Chemical and biological investigations of extracts from the sponge genus Auletta and two collections of Siphonochalina sp. have shown these organisms to be producers of the potent hemiasterlin class of antitumor agents. In addition to the previously known hemiasterlin (1) and hemiasterlin A (2), a new analogue, hemiasterlin C (3), was isolated and identified. The structures of 1 and 2 were assigned based on comparison to literature values, and 3 was identified on the basis of 1H NMR, 13C NMR, COSY, HSQC, and HMBC experiments. The cytotoxic and antitubulin activities of 1-3 were evaluated. In a comparative assay for inhibition of tubulin polymerization, the hemiasterlins were more potent than dolastatin 15 and equipotent with cryptophycin 1, but were somewhat less potent than dolastatin 10.     

Alkamides from the fruits of Piper longum and Piper nigrum displaying potent cell adhesion inhibition

Eight alkamides 1-8 were isolated by bioassay-guided isolation of EtOH extracts of the fruits of Piper longum and Piper nigum (Piperaceae). Their structures were elucidated by spectroscopic analysis ((1)H, (13)C NMR, and ESI-MS) as follows: guineensine (1), retrofracamide C (2), (2E,4Z,8E)-N-[9-(3,4-methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (3), pipernonaline (4), piperrolein B (5), piperchabamide D (6), pellitorin (7), and dehydropipernonaline (8). Their compounds 3-5, 7, and 8 inhibited potently the direct binding between sICAM-1 and LFA-1 of THP-1 cells in a dose-dependent manner, with IC(50) values of 10.7, 8.8, 13.4, 13.5, and 6.0 microg/mL, respectively.