Cytotoxic constituents of <Emphasis Type="Italic">Amanita subjunquillea</Emphasis>

As part of our systematic study of Korean toxic mushrooms, we have investigated the constituents of Amanita subjunquillea. The column chromatographic separation of the MeOH extract of A. subjunquillea led to the isolation of four ergosterols, two cerebrosides and four cyclopeptides. Their structures were determined by spectroscopic methods to be (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9,22-triene-3beta-ol (1), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (2), (22E,24R)-5alpha,6alpha-epoxyergosta-8,22-diene-3beta,7beta-diol (3), (24S)-ergost-7-en-3beta-ol (4), 8,9-dihydrosoyacerebroside I (5), soyacerebroside I (6), beta-amanitin (7), phalloin (8), alpha-amanitin (9), and phalloidin (10). The compounds 1-6 and 8 were isolated for the first time from this mushroom. The isolated compounds were evaluated for the cytotoxicity against A549, SK-OV-3, SK-MEL-2 and HCT15 cells. Compound 9 exhibited significant cytotoxic activity against A549, SK-OV-3, SK-MEL-2 and HCT15 with ED(50) values of 1.47, 0.26, 1.57 and 1.32 microM, respectively.     

Cerebrosides and terpene glycosides from the root of<Emphasis Type="Italic">aster scaber</Emphasis>

Three cerebrosides 2, 3, and 5 and two terpene glycosides 1 and 4 have been isolated from the methanol extract of the root of Aster scaber. Their structures were determined as 3-O-beta-D-glucuronopyranosyl-oleanolic acid methyl ester (1), (2S, 3S, 4R, 2'R, 8Z, 15'Z)-N-2'-hydroxy-15'-tetracosenoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (2), (2S, 3S, 4R, 8Z)-N-octadecanoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (3), 1alpha-hydroxy-6beta-O-beta-D-glucosyl-eudesm-3-ene (4), and (2S, 3S, 4R, 2'R, 8Z)-N-2'-hydroxy-hexadecanoyl-1-O-beta-D-glucopyranosyl-4-hydroxy-8-sphingenine (5) on the basis of spectroscopic methods.     

A new sesquiterpene lactone from<Emphasis Type="Italic">Artemisia rubripes</Emphasis> nakai

The chromatographic separation of a methylene chloride extract of Artemisia rubripes led to the isolation of a new sesquiterpene lactone (3), together with four known compounds, a coumarin (2) and three terpenes (1, 4, and 5). Their structures were characterized to be 1beta,6alpha-dihydroxy-4(15)-eudesmene (1), scopoletin (2), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,10(14), 11(13)-triene-6,12-olide (3), 1alpha,4beta-dihydroxy-8alpha-acetoxy-guaia-2,9,11(13)-triene-6,12-olide (4), and beta-sitosterol-3-O-beta-D-glycoside (5) by spectroscopic means.     

Flavonoids and aromatic compounds from the rhizomes of<Emphasis Type="Italic">Zingiber zerumbet</Emphasis>

Repeated column chromatography of the CHCl3-soluble fraction of Zingiber zerumbet led to the isolation and identification of two aromatic compounds, p-hydroxybenzaldehyde (1) and vanillin (2), and six kaempferol derivatives, kaempferol-3,4',7-O-trimethylether (3), kaempferol-3-O-methylether (4), kaempferol-3,4'-O-dimethylether (5), 4'-O-acetylafzelin (6), kaempferol-3-O-(4-O-acetyl-alpha-L-rhamnopyranoside)], 2',4'-O-diacetylafzelin (7), kaempferol-3-O-(2,4-O-diacetyl-alpha-L-rhamnopyranoside)], and 3',4'-O-diacetylafzelin (8), kaempferol-3-O-(3,4-O-diacetyl-alpha-L-rhamnopyranoside)]. The structures of 1-8 were identified by analysis of spectroscopic data as well as by comparison with published values. This is the first report on the isolation of compounds 1-3 from this plant.     

Two new phenolic constituents of<Emphasis Type="Italic">Humulus japonicus</Emphasis> and their cytotoxicity test<Emphasis Type="Italic">In Vitro</Emphasis>

Two new phenolic constituents (4 and 6), together with four known constituents, methyl ferulate (1), eugenyl-beta-D-glucopyranoside (2), apigenin-7-O-beta-D-glucopyranoside (3), and (E)-resveratrol-3-O-beta-D-glucopyranoside (5) were isolated from the MeOH extract of the aerial part sof Humulus japonicus. The structures of the new compounds were determined by spectroscopic methods to be divarin-3-O-beta-glucopyranoside (4), and lariciresinol-9-O-beta-xylopyranoside (6). Compounds 1 and 3 exhibited moderate cytotoxicity against two human cancer cell lines (SK-OV-3 and HCT15) with ED50 values ranging from 8.84 to 8.79 microM.     

A benzenoid from the stem of<Emphasis Type="Italic">Acanthopanax senticosus</Emphasis>

Seven compounds were isolated from the stem of Acanthopanax senticosus by repeated column chromatography. Their structures were elucidated as isovanillin (1), (-)-sesamin (2), isofraxidin (3), (+)-syringaresinol (4), 5-hydroxymethylfurfural (5), eleutheroside B (6), and eleutheroside E (7) by spectral analysis. Among them, isovanillin (1) was isolated for the first time from the family Araliaceae.     

Norditerpenoid alkaloids and other components from the processed tubers ofaconitum carmichaeli

A new norditerpenoid and a known alkaloid were isolated from the alkaloidal fraction of the processed tubers of Aconitum carmichaeli. The structure of the new norditerpenoid alkaloid was elucidated as lipoforesaconitine (1) on the basis of spectroscopic analysis. The known norditerpenoid alkaloid was characterized as lipoyunanaconitine (2). In addition, a new flavonoid, 6"-O-acetylliquiritin (7), along with a known ceramide, (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxylignoceroylamino]-8(E)-octadecene-1,3,4-triol (3), as well as a known steroid saponin, gracillin (8), and three known flavonoids, liquiritigenin (4), isoliquiritigenin (5), and liquiritin (6), were also isolated and characterized. All known compounds were isolated from this plant for the first time. The structures of the isolates were established by spectroscopic and chemical methods.     

Cerebrosides from longan arillus

From the pulp of Euphoria longana (Longan Arillus), three cerebroside molecular species have been isolated. Six known cerebrosides, soyacerebrosides I and II, 1-O-beta-D-glucopyranosyl-(2S,3R,4E,8E)-2-(2'-lignoceroylamino)-4,8-octadecadiene-1,3-diol (longan cerebroside I) and its 8Z isomer (longan cerebroside II), momor-cerebroside I, and phytolacca cerebroside, were identified as major components of these cerebroside molecular species. All the cerebrosides were shown to be a mixture of geometrical isomers (8E and 8Z) of sphingosine-type or phytosphingosine-type glucocerebrosides possessing 2-hydroxy fatty acids. The structures of these cerebrosides have been determined on the basis of chemical and spectroscopic evidence.     

Phytochemical constituens of<Emphasis Type="Italic">Cirsium setidens</Emphasis> Nakai and their cytotoxicity against human cancer cell lines

Five terpenes (1-5), three fatty acids (6-8), two sterols (9 and 11), and a monogalactosyldiacyl glycerol (10) were isolated from the methylene chloride extract of the aerial part of Cirsium setidens. Their chemical structures were determined to be alpha-tocopherol (1), 25-hydroperoxycycloart-23-en-3beta-ol (2), 24-hydroperoxycycloart-25-en-3beta-ol (3), mokko lactone (4), transphytol (5), 9,12,15-octadecatrienoic acid (6), 9,12-octadecadienoic acid (7), hexadecanoic acid (8), acylglycosyl beta-sitosterol (9), (2R)-1,2-O-(9z,12z,15z-dioctadecatrienoyl)-3-O-beta-D-galactopyranosyl glycerol (10) and beta-sitosterol glucoside (11) by spectral evidences. Compound 3 exhibited significant cytotoxic activity against five human cancer cell lines with its ED50 values ranging from 2.66 to 11.25 microM.     

A new lignan glycoside from the fruits of <Emphasis Type="Italic">Cornus kousa</Emphasis> Burg.

A new lignan glycoside, (7'S, 8'R)-dihydrodehydrodiconiferyl alcohol-4'-O-beta-D-xylopyranoside (1), named cornuskoside A, was isolated from the fruits of Cornus kousa. The structure of the compound was determined by spectroscopy, including FABMS, UV, IR, (1)H-and 13C-NMR, DEPT and 2D-NMR (COSY, HSQC, and HMBC). This new lignan glycoside, along with its aglycone, (7'S, 8'R)-dihydrodehydrodiconiferyl alcohol (3), and another lignan with a similar skeleton, (-)-balanophonin (2), which have been previously isolated from this plant, were evaluated for cytotoxicity in human cancer cell lines such as HeLa, MCF-7, SK-MEL-5, and SK-OV-3. Compounds 2 and 3 showed cytotoxicity against HeLa [IC50 = 29.1 microM (2), 45.5 microM (3)], MCF-7 [IC50 = 29.2 microM (2), 28.2 microM (3)], SK-MEL-5 [IC50 = 31.3 microM (2), 32.3 microM (3)], and SK-OV-3 [IC50 = 33.4 microM (2), 43.4 microM (3)] cell lines.     

Cytotoxic constituents of the octocoralDendronephthya gigantea

A known monoalkyl glycerol ether, (+/-)-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.     

Terpene and phenolic constituents of <Emphasis Type="Italic">Lactuca indica</Emphasis> L.

We isolated seven terpenes and five phenolic constituents from the aerial parts of Lactuca indica L. using column chromatographic separation of its MeOH extract. Their structures were determined by spectroscopic methods to be trans-phytol (1), 3beta-hydroxyglutin-5-ene (2), 5,6-epoxy-3-hydroxy-7-megastigmen-9-one (3), 11beta-13-dihydrolactucin (4), 2-phenylethyl beta-D-glucopyranoside (5), cichorioside B (6), 1-hydroxylinaloyl-6-O-beta-D-glucopyranoside (7), (6S,9S)-roseoside (8), benzyl-beta-D-glucopyranoside (9), 2-(3'-O-beta-D-glucopyranosyl-4'-hydroxyphenyl)-ethanol (10), 3-(beta-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-dihydrobenzofuran (11), and (+)-taraxafolin-B (12). Compounds 1-3, 5, and 7-12 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.     

Isolation of limonoids and alkaloids from<Emphasis Type="Italic">Phellodendron amurense</Emphasis> and their multidrug resistance (MDR) reversal activity

Three limonoids and five alkaloids were isolated from the chloroform layer of the MeOH extract of the bark of Phellodendron amurense (Rutaceae). The structures of the compounds isolated were determined to be obacunone (1), limonin (2), 12alpha-hydroxylimonin (3), gamma-fagarine (4), oxyberberine (5), canthin-6-one (6), 4-methoxy-N-methyl-2-quinolone (7) and oxypalmatine (8) based on the physicochemical and spectroscopic data. Compounds 3, 5, 7, and 8 were first isolated from the Phellodendron amurense. The isolated compounds were then tested for their cytotoxicity against five human tumor cell lines in vitro using the SRB method. Compound 5 showed significant cytotoxicity against the five tumor cell lines with ED50 values ranging from 0.30 to 3.0 microg/mL. The marginal or noncytotoxic compounds (1, 2, 3, 4, and 7) were examined for their P-gp related MDR reversal activities. Compound 1 showed significant P-gp MDR inhibition activity in MES-SA/DX5 and HCT15 cells with an ED50 value of 0.028 microg/mL and 0.0011 microg/mL, respectively.     

Cytotoxic ergosterols from Paecilomyces sp. J300

Seven ergosterol derivatives (1-7) were isolated from silkworm larvae infected with Paecilomyces sp. J300. On the basis of spectroscopic means, their structures have been elucidated as 3beta,5alpha-dihydroxy-ergosta-7,22-diene (1), 5alpha,6alpha-epoxy-(22E,24R)-ergosta-8(14), 22-diene-3beta, 7alpha-diol (2), 5alpha,6alpha-epoxy-(22E,24R)-ergosta-8,22-diene-3beta,7alpha-diol (3), ergosta-4,6,8(14),22-tetraene-3-one (4), ergosterol (5), ergosterol endoperoxide (6), 3beta,5alpha-dihydroxy-6beta-methoxyergosta-7,22-diene (7). Compounds 3-7 showed moderate cytotoxicity against five tumor cells.     

Constituents from the fruiting bodies ofGanoderma applanatum and their aldose reductase inhibitory activity

Eight compounds were isolated from the fruiting bodies of Ganoderma applanatum, and were identified as 2-methoxyfatty acids (1), 5-dihydroergosterol (2), ergosterol peroxide (3) 3beta,7beta, 20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (4), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (5), cerevisterol (6), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E (22)-dien-26-oic acid (7), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (8) by spectral analysis. All compounds were isolated for the first time from this fruiting bodies, and their effect on rat lens aldose reductase (RLAR) activity was tested. Among these eight compounds, ergosterol peroxide (3) was found to exhibit potent RLAR inhibition, its IC50 value being 15.4 microg/mL.     

New prenylated flavones from <Emphasis Type="Italic">Artocarpus champeden</Emphasis>, and their antimalarial activity in vitro

Two new prenylated flavones, artocarpones A and B (1 and 2), and seven known isoprenylated flavonoids, artonin A (3), cycloheterophyllin (4), artoindonesianin E (5), artoindonesianin R (6), heterophyllin (7), heteroflavanone C (8), and artoindonesianin A-2 (9), have been isolated from the stem bark of Artocarpus champeden. Their structures were determined by spectroscopic analysis. Among the compounds isolated, 8 had the most potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with an IC₅₀ value of 1 nmol L⁻¹.     

Pytochemical constituents of the aerial parts from<Emphasis Type="Italic">solidago virga-aurea var. gigantea</Emphasis>

The chromatographic separation of the MeOH extract of the aerial parts of Solidago virga-aurea var. gigantea M(IQ) (Compositae) led to the isolation of six terpenoids and four phenolic compounds, trans-phytol (1), ent-germacra-4(15),5,10(14)-trien-1alpha-ol (2), beta-amyrin acetate (3), ent-germacra-4(15),5,10(14)-trien-1beta-ol (4), beta-dictyopterol (5), oleanolic acid (6), kaempferol (7), kaempferol-3-O-rutinoside (8), methyl 3,5-di-O-caffeoyl quinate (9), and 3,5-di-O-caffeoyl quinic acid (10). Their structures were established by chemical and spectroscopic methods. Compounds 4, 5, and 10 showed moderate cytotoxicity against five cultured human tumor cell lines in vitro with its ED50 values ranging from 1.52 to approximately 18.57 microg/mL.     

Platelet anti-aggregatory effects of coumarins from the roots of<Emphasis Type="Italic">Angelica genuflexa</Emphasis> and<Emphasis Type="Italic">A. gigas</Emphasis>

Five coumarins, isoimperatorin (1), pabulenol (2), isooxypeucedanin (3), oxypeucedanin hydrate (4) and osthol (5) were isolated from the MeOH extract of Angelica genuflexa in the course of searching for anti-platelet and anti-coagulant components from plants. Pabulenol (2) was isolated from A. genuflexa for the first time. The five compounds isolated from A. genuflexa, together with decursinol angelate (6), decursin (7) and nodakenin (8) from A. gigas were evaluated for their effects on platelet aggregation and blood coagulation. Compounds 2, 5, 6 and 7 were observed to be either equally effective or 2-4 times more inhibitory than ASA in both arachidonic acid and U46619 (TXA2 mimetic) induced platelet aggregations.     

A sphingolipid and tyrosinase inhibitors from the fruiting body of<Emphasis Type="Italic">phellinus linteus</Emphasis>

This paper for the first time reports the isolation of 5 compounds from Phellinus linteus. A sphingolipid (1) and two tyrosinase inhibitory compounds (2, 3) along with two carboxylic acids (4, 5), were isolated from the fruiting body of Phellinus linteus (Berk & Curt) Aoshima. The structure of compound 1 was identified as 1-omicron-beta-D-glucopyranosyl-(2S, 3R, 4E, 8E)-2-[(2R)-2-hydroxyhexadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol, known as cerebroside B, based on spectroscopic methods such as 1 D and 2D NMR as well as by acid hydrolysis. Compounds 2 -5 were identified as protocatechualdehyde (2), 5-hydroxymethyl-2-furaldehyde (HMF) (3), succinic acid (4), and fumaric acid (5) based on the spectroscopic evidence. Compounds 2 and 3 inhibited the oxidation of L-tyrosine catalyzed by mushroom tyrosinase with an IC50 of 0.40 and 90.8 microg/mL, respectively. The inhibitory kinetics, which were analyzed by the Lineweaver-Burk plots, were found to be competitive and noncompetitive inhibitors with a Ki of 1.1 microM and 1.4 mM, respectively.     

Isocoumarin derivatives from the sea squirt-derived fungus penicillium stoloniferum QY2-10 and the halotolerant fungus penicillium notatum B-52

Two isocoumarin derivatives, stoloniferol A (1) and B (2), a known 5alpha, 8alpha-epidioxy-23-methyl-(22E, 24R)-ergosta-6, 22-dien-3beta-ol (3), and a known dihydrocitrinone (4) were isolated from the ethyl acetate extract of the sea squirt-derived fungus, Penicillium stoloniferum QY2-10, and a halophilic fungus, Penicillium notatum B-52, respectively. Their structures were elucidated by spectroscopic methods and optical rotation. The stereochemistry of 2 was determined on the basis of different NOE experiments and chemical transformation. Compound 3 showed cytotoxicity against P388 cells, with an IC50 value of 4.07 microM.