Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

A new ceramide from <Emphasis Type="Italic">Ramaria botrytis</Emphasis> (Pers.) Ricken

A new ceramide, (2S,2′R,3R,4E,8E)-N-2′-hydroxyoctadecanoyl-2-amino-9-methyl-4,8-heptadecadiene-1,3-diol (1), was isolated together with four known sterols, 5α,6α-epoxy-3β-hydroxy-(22E)-ergosta-8(14),22-dien-7-one (2), ergosterol peroxide (3), cerevisterol (4) and 9α-hydroxycerevisterol (5), from the fruiting bodies of Ramaria botrytis (Pers.) Ricken (Ramariaceae). The structure of the new compound was elucidated based on spectral data.     

Iridoid glucoside, (3<Emphasis Type="Italic">R</Emphasis>)-oct-1-en-3-ol glycosides,and phenylethanoid from the aerial parts of <Emphasis Type="Italic">Caryopteris incana</Emphasis>

Eleven compounds of interest were isolated from the aerial parts of Caryopteris incana, specifically a new acyl derivative (3) of 8-O-acetylharpagide, two new (3R)-oct-1-en-3-ol glycosides (5, 6), and 6-O-caffeoylphlinoside A (11) along with seven known compounds, 8-O-acetylharpagide (1), 6′-O-p-coumaroyl-8-O-acetylharpagide (2), (3R)-oct-1-en-3-ol (matsutake alcohol) O-α-l-arabinopyranosyl-(1″ → 6′)-O-β-d-glucopyranoside (4), apigenin 7-O-neohesperidinoside (7), 6′-O-caffeoylarbutin (8), and two phenylethanoids, leucosceptoside A (9) and phlinoside A (10). This paper deals with structural elucidation of the new compounds.     

Studies on the constituents from the fruits of <Emphasis Type="Italic">Phaleria macrocarpa</Emphasis>

From the fruits of Phaleria macrocarpa, icariside C₃ (1), phalerin (2), and mangiferin (3) were isolated and their structures were identified on the basis of spectroscopic data. Icariside C₃ (1) showed a slow vasorelaxant activity against noradrenaline-induced contraction of isolated rat aorta. The structure of phalerin (2) was revised as 2,4′,6-trihydroxy-4-methoxybenzophenone-2-O-β-d-glucoside.     

Constituents of the roots of <Emphasis Type="Italic">Ligularia dentata</Emphasis> Hara

Nine known compounds, butyrospermol (1), lupeol (2), stigmast-4-en-3-one (3), stigmast-4-ene-3,6-dione (4), (+)-methyl abscisate (5), methyl indole-3-carboxylate (6), vanillin (7), methyl (E)-caffeate (8), and methyl (E)-ferulate (9), and two new compounds, methyl (E)-feruloylglycolate (10), and methyl-7,8-dihydro-(S)-7-methoxyferulate (11), have been isolated from the roots of Ligularia dentata Hara (Compositae). The structures were elucidated on the basis of spectral data.     

A new prenylated dihydrochalcone from the leaves of <Emphasis Type="Italic">Artocarpus lowii</Emphasis>

A new prenylated dihydrochalcone, 2′,4′-dihydroxy-4-methoxy-3′-prenyldihydrochalcone (1), along with two known compounds, 2′,4′,4-trihydroxy-3′-prenylchalcone (2) and 2′,4-dihydroxy-3′,4′-(2,2-dimethylchromene)chalcone (3) were isolated from the leaves of Artocarpus lowii. The structures of 1–3 were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compounds 1–3 showed strong free radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) measured by electron spin resonance (ESR) spectrometry.     

CYP3A4 inhibitors isolated from a marine derived fungus <Emphasis Type="Italic">Penicillium</Emphasis> species

More than 50% of clinically used drugs are thought to be metabolized by cytochrome P450 (CYP) 3A4. Discovery of new, inexpensive, CYP3A4 inhibitors will reduce drug dosages needed to cure patients. In our search for new inhibitors of the enzyme CYP3A4, extracts from 102 marine fungi were screened. Seven of the extracts had potent CYP3A4 inhibitory activity. Four aromatic compounds were isolated from an extract of a culture of one of these, a Penicillium sp., and were identified as 3-methoxyphenol (1), 4-methoxyphenylacetic acid (2), 4-(2-hydroxyethyl)phenol (3), and 4-hydroxy-2-methoxyacetanilide (4) by use of spectroscopic data. Interestingly, compound 3 at 250 μg mL⁻¹did not inhibit CYP3A4 whereas compounds 1, 2 and 4 had CYP inhibitory activity with IC₅₀ values of 2.0, 1.6 and 0.41 μg mL⁻¹, respectively.     

A new kaempferol trioside from <Emphasis Type="Italic">Solidago altissima</Emphasis> L.

A new kaempferol trioside [kaempferol 3-O-rutinoside 7-O-β-d-apiofuranoside, (1)] was isolated together with nine phenolic compounds, trans-tiliroside (2), caffeic acid (3), chlorogenic acid (4), 3-O-caffeoylquinic acid (5), 4-O-caffeoylquinic acid (6), 3-O-coumaroylquinic acid (7), 4-O-coumaroylquinic acid (8), 3,5-di-O-caffeoylquinic acid (9) and 4,5-dicaffeoylquinic acid (10) from the leaves of Solidago altissima L. The structure elucidations of the compounds were based on the analyses of spectroscopic data.     

Antioxidative iridoid glycosides and phenolic compounds from <Emphasis Type="Italic">Veronica peregrina</Emphasis>

Eight iridoid glycosides and four phenolic compounds were isolated from the EtOAc soluble fraction of Veronica peregrina MeOH extract as the radical scavengers for antioxidant activity. The compounds were identified as protocatechuic acid (1), luteolin (2), veronicoside (3), minecoside (4), specioside (5), amphicoside (6), catalposide (7), 6-O-cis-p-coumaroyl catalpol (8), p-hydroxy benzoic acid methyl ester (9), verproside (10), verminoside (11), and chrysoeriol 7-glucuronide (12) by spectroscopic analysis. All compounds except for 1 and 2 were isolated for the first time from this plant. The antioxidant activity was evaluated by the ORAC(Oxygen Radical Absorbance Capacity) assay, which measures scavenging activity against peroxy radicals induced by 2,2′-azobis (2-methoxypropion-amidine) dihydrochloride, and the ORAC value is expressed as relative trolox equivalent. Compounds 2, 4, 5, 6, 8, and 12 exhibited potent antioxidant activity, and compounds 1, 11 had similar activity with trolox, whereas the other compounds showed weaker activity than trolox.     

Two new neolignan glycosides from leaves of <Emphasis Type="Italic">Osmanthus heterophyllus</Emphasis>

Two new neolignan glycosides, (7R, 8R)-threo-guaiacylglycerol-8-O-4′-sinapyl ether 7-O-β-d-glucopyranoside (1) and (7S, 8R)-5-methoxydehydrodiconiferyl alcohol 4-O-β-d-glucopyranoside (2), and four known ones (3–6), were isolated from the leaves of Osmanthus heterophyllus. The structures of compounds 1–6 were established on the basis of spectral and chemical data.     

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.     

Secoiridoid glycosides from the leaves of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> subsp. <Emphasis Type="Italic">serrata</Emphasis>

Seven secoiridoid glycosides, secologanin dimethyl acetal (1), n-butyl vogeloside (2), n-butyl epi-vogeloside (3), (7R)-n-butyl morroniside (4), hydrangenoside A (5), hydrangenoside C (6), and hydrangenoside A dimethyl acetal (7), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (Thunb.) Makino (Saxifragaceae). The structures were elucidated on the basis of spectral data.     

A new triterpenoid from <Emphasis Type="Italic">Panax ginseng</Emphasis> exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line

A new triterpenoid, 20(R),22(ξ),24(S)-dammar-25(26)-ene-3β,6α,12β,20,22,24-hexanol (1), and three known triterpenoids, β-D-glucopyranoside,(3β,12β)-12,20-dihydroxydammar-24-en-3-yl,6-acetate (2), 20(R)-ginsenoside Rg₃ (3), and 20(R)-ginsenoside Rh₂ (4), were isolated from the leaves of Panax ginseng. Their structures were determined by chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-ESI-MS). Compounds 1–4 were exhibited various degrees of cytotoxicity in the human hepatoma cell line, HepG2. Compound 1 had the highest cytotoxic potency, with an IC₅₀ value of 20.1 μM, by stimulating p53-mediated cell cycle arrest at the G1 to S phase transition, leading to apoptosis via activation of the caspase signaling pathway.     

Triterpenoic acids of Prunella vulgaris var. lilacina and their cytotoxic activities In Vitro

The column chromatographic separation of the MeOH extract from the aerial parts of Prunella vulgaris var. lilacina Nakai led to the isolation of fifteen triterpenoic acids (2–6, 9–13, 16–20), four flavonoids (14, 21–23), four phenolics (7, 8, 15, 24), and a diterpene (1). Their structures were determined by spectroscopic methods to be trans-phytol (1), oleanic acid (2) ursolic acid (3), 2α,3α,19α-trihydroxyurs-12en-28oic acid (4), 2α,3α-dihydroxyurs-12en-28oic acid (5), maslinic acid (6), caffeic acid (7), phydroxy cinnamic acid (8), 2α,3α,19α,23-tetrahydroxyurs-12en-28oic acid (9), 2α,3α,23-trihydroxyurs-12en-28oic acid (10), 2α,3β-dihydroxyurs-12en-28oic acid (11), 2α,3β,24-trihydroxyolea-12en-28oic acid (12), (12R, 13S)-2α,3α,24,trihydroxy-12,13-cyclo-taraxer-14-en-28oic acid (13), quercertin 3-O-β-D-glucopyranoside (14), rosmarinic acid (15), 2α,3α,24-trihydroxyurs-12,20(30)-dien-28oic acid (16), 2α,3α,24-trihydroxyolea-12en-28oic acid (17), 2α,3β,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-Dglucopyranoside (18), 2α,3α,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-D-glucopyranoside (19), prunvuloside A (20), kaempferol 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopranoside (21), kaempferol 3-O-β-D-glucopyranoside (22), quercertin 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside (23), and 2-hydroxy-3-(3’,4’-dihydroxyphenly)propanoic acid (24). Compounds 1, 8–12, 17, 21, 23, and 24 were isolated from this plant source for the first time. The isolated compounds were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells in vitro using the sulforhodamin B bioassay (SRB) method. Compound 3 exhibited moderate cytotoxic activity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells, with ED₅₀ values of 3.71, 3.65, 13.62, and 5.44 μM, respectively.     

Promotion of IL-8 production in PMA-stimulated HL-60 cells by sesquiterpene quinones from a marine sponge, <Emphasis Type="Italic">Hippospongia</Emphasis> sp.

An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC₅₀ values between 0.6 and 2.8 μmol L⁻¹. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60 cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone (1) and its 5 epimer (2) had similar activity against V79 cells (EC₅₀ = 2.8 and 2.3 μmol L⁻¹, respectively) but did not modulate IL-8 production even at 10 μmol L⁻¹. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 μmol L⁻¹, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC₅₀ = 0.6, 1.7, and 0.8 μmol L⁻¹, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC₅₀ = 0.8, 2.3, and 2.0 μmol L⁻¹, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first report of modulation of IL-8 production by these sesquiterpene quinones.     

Stilbene and dihydrophenanthrene derivatives from <Emphasis Type="Italic">Pholidota chinensis</Emphasis> and their nitric oxide inhibitory and radical-scavenging activities

Two new stilbene derivatives, (E)-2′,3,3′-trihydroxy-5-methoxystilbene (1, Pholidotol C) and (Z)-3,3′-hydroxy-5-methoxystilbene (2, Pholidotol D), were isolated from the air-dried whole plant of Pholidota chinensis Lindl., together with eight known dihydrophenanthrene derivatives, lusianthridin (3), cannabidihydrophenanthrene (4), coelonin (5), hircinol (6), erianthridin (7), 4,5-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (8), eulophiol (9), and 2,4,7-trihydroxy-9,10-dihydrophenanthrene (10), and a benzoxepin derivative bulbophylol B (11). Their inhibitory effects on nitric oxide (NO) production activity and 1,1-diphenyl-2-picrylhydrazil radical-scavenging activity were examined. Among these compounds, 11 exhibited the most potent activity toward NO production inhibition activity and radical-scavenging activity; moreover, 11 reduced inducible nitric oxide synthase mRNA expression.     

Sesquiterpene components from the flower buds ofMagnolia fargesii

From the Chinese crude drugshin-i, the flower buds ofMagnolia fargesii, four sesquiterpene, oplopanone (1), oplodiol (2), homalomenol A (3) and 1β,4β,7α-trihydroxyeudesmane (4) were isolated. These structures were elucidated and the¹³C-NMR chemical, shifts of these compounds were revised by means of various 2D-NMR techniques.     

Antibacterial activity of <Emphasis Type="Italic">Capsicum annuum</Emphasis> extract and synthetic capsaicinoid derivatives against <Emphasis Type="Italic">Streptococcus mutans</Emphasis>

The inhibitory effects of the ethyl acetate extract and capsaicin (1) and dihydrocapsaicin (2) isolated from fruits of Capsicum annuum chili pepper type, and synthetic capsaicinoid derivatives (N-(4-hydroxyphenylethyl)decamide (3), (E)-N-(4-hydroxy-3-methoxybenzyl)-3,7-dimethylocta-2,6-dienamide (4), 4-hydroxy-3-methoxy-N-((E)-3,7-dimethylocta-2,6-dienyl)benzamide (5) and N-(4-hydroxy-3-methoxybenzyl)decamide (6) at different concentrations were evaluated against Streptococcus mutans. The minimum inhibitory concentration at which the ethyl acetate extract prevented the growth of S. mutans was 2.5 mg/mL; those of the isolated compounds 1 and 2 were 1.25 μg/mL, while 3 was 5.0 μg/mL, and 4, 5 and 6 were 2.5 μg/mL, respectively.     

Two new phenolic glycosides from <Emphasis Type="Italic">Syringa reticulata</Emphasis>

Two new phenolic glycosides—3′-O-β-d-glucopyranosysalidroside (1) and cis-echinacoside (2)—together with four known ones—forsythoside B (3), decaffeoylacteoside (4), osmanthuside F (5) and (−)-olivil-4′-O-β-d-glucopyranoside (6)—were isolated from the leaves of Syringa reticulata. Their structures were established on the basis of spectral and chemical data.     

A new erythrinan alkaloid from the seed of <Emphasis Type="Italic">Erythrina addisoniae</Emphasis>

Phytochemical study on the EtOAc extract of the seed of Erythrina addisoniae (Leguminosae) resulted in the isolation of a new erythrinan alkaloid, erysovine-N-oxide (1), along with eight known alkaloids, erysosalvinone (2), erysodine (3), 1H-indole-3-propanamide (4), glucoerysodine (5), erysotrine (6), erysovine (7), erythraline (8) and erysopine (9). Their chemical structures were identified on the basis of physicochemical and spectroscopic analyses.