Carbazole alkaloids as new cell cycle inhibitor and apoptosis inducers from Clausena dunniana Levl

Carbazole alkaloids, 3-methylcarbazole (1), murrayafoline A (2), girinimbine (3), mahanimbine (4) and bicyclomahanimbine (5), were isolated for the first time from Clausena dunniana Levl. by bioassay-guided separation procedure and were identified by spectroscopic methods. Compounds 1 - 5 showed growth inhibitory activity (1, IC₅₀ 25 μg/ml) on human fibrosarcoma HT-1080 cells and cell cycle M-phase inhibitory (2, MIC 0.78 μg/ml) and apoptosis inducing (2, MIC 1.56 μg/ml; 3, MIC 25 μg/ml; 4, MIC 20 μg/ml; 5, MIC 30 μg/ml) activities on mouse tsFT210 cells, respectively, and 2 - 5 provided the first examples of carbazole alkaloids as new cell cycle inhibitors and apoptosis inducers.     

Seven new meroditerpenoids, from the marine sponge Strongylophora strongylata, that inhibited the maturation of starfish oocytes

Seven new meroditerpenoids, strongylophorines 13-19 (1-7), have been isolated together with the four known strongylophorines 2 (8), 3 (9), 4 (10), and 8 (11) by a screening method using oocytes of the starfish Asterina pectinifera from a marine sponge Strongylophora strongylata collected at Iriomote Island, Okinawa, Japan. The structures were assigned according to their spectral data. Ten strongylophorines inhibited the maturation of starfish oocytes in the range 1.1-37.6 μM (IC₅₀), while strongylophorine 4 (10) was not active at 250 μM.     

Cytotoxic ent-kauranoids from Isodon leucophyllus

Two new compounds, baiyecrystals D and E (1, 2), together with eight known analogues, xerophilusin B (4), macrocalin B (5), oridonin (6), rosthorin A (7), lasiocarpanin (8), rabdoternin A (9) and phyllostachysin A (10) and B (11), were isolated from the aerial parts of Isodon leucophyllus. The structures of 1 and 2 and 4-11 were elucidated on the basis of spectroscopic methods, especially the 2D NMR spectral analysis. Compounds 2, 6-8 and 10 were evaluated for their antineoplastic activities in vitro. Among them, lasiocarpanin (8) showed significant inhibitory activities against K562 and Bcap37 cells, with the IC₅₀ values of 0.13 and 1.26 μg mL_-1, respectively, which were lower than those of the positive control.     

Triterpenes from Tripterygium wilfordii Hook

Two new friedelane-type triterpenes, tripterfrielanons A (1) and B (2), along with six known triterpenoids, friedelin (3), canophyllal (4), canophyllalic acid (5), 3-oxo-29-hydroxyfriedelane (6), wilforlide A (7), wilforlide B (8), have been isolated from the EtOH extract of the roots of Tripterygium wilfordii Hook.f. Compounds 4, 5, 6 were isolated for the first time from this plant. The new triterpenes 1 and 2 exhibited mild cytotoxic activity against human Hela cell lines in vitro. The assay showed the IC₅₀ of 1 and 2 were 8.5 and 25 μg/mL, respectively.     

Antibacterial constituents from Stemona sessilifolia

Bioassay-guided fractionation led to the isolation of eight compounds from Stemona sessilifolia. Of the eight isolates, three new bibenzyls, stilbostemins M-O (1-3), and a new tocopherol, 6-methoxy-3,4-dehydro-δ-tocopherol (4) were revealed together with four known compounds 3,5-dihydroxy-2'-methoxy bibenzyl (5), 3,5-dihydroxy bibenzyl (6), β-tocopherol (7), and γ-tocopherol (8). Compounds 5, 6, and 8 exhibited strong antibacterial activities against Staphylococcus aureus and S. epidermidis.     

Two new 18-carbon norditerpenoid alkaloids from Aconitum sinomontanum

Two new 18-carbon norditerpenoid alkaloids, sinaconitines A (1) and B (2), together with two known alkaloids, ranaconitine (3) and lappaconitine (4), were isolated from the roots of Aconitum sinomontanum. Their structures were elucidated on the basis of spectral evidences and X-ray crystallographic analysis for 1. Furthermore, the reversed ¹³C NMR assignments for C-10 and C-13 of 3, 4, puberanine, puberanidine and demethyllappaconitine were revised. Compounds 1-4 were evaluated for cyclooxygenase-2 (COX-2) enzyme inhibitory activity. However, they did not show any inhibition at 10 μM.     

9, 10-Dihydrophenanthrene derivatives from Pholidota yunnanensis and scavenging activity on DPPH free radical

Three new 9,10-dihydrophenanthrene derivatives named phoyunnanins A-C, together with six known 9,10-dihydrophenanthrene constituents, 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene (4), lusianthridin (5), eulophiol (6), 2,4,7-trihydroxy-9,10-dihydrophenanthrene (7) and imbricatin (8), were isolated from the 60% ethanolic extract of air-dried whole plant of Pholidota yunnanensis Rolfe. The structures of phoyunnanins A-C were established as 6-[2'-(3',3'-dihydroxy-5'-methoxybibenzy)]-4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (1), 6-[6'-(trans-3',3'-dihydroxy-5'-methoxystilbeny)]-4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (2) and 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10,10'-tetrahydro-1,6'-biphenanthrene (3), respectively, on the basis of the spectroscopic analysis. All eight compounds (1-8) were found to show the DPPH free radical scavenging activity with EC₅₀ from 8.8 to 55.9 μM.     

Three new isoprenylated flavonoids from the roots of Sophora flavescens

Three new flavonoids isoprenylated as 2,2-dimethyl-dihydropyran groups, named sophoranodichromanes A-C (1-3), have been isolated from the roots of Sophora flavescens, together with the known compounds, chrysophanol (4), soyasapogenol B (5) and β-sitosterol (6). Their structures have been elucidated by spectroscopic methods.     

Chemical constituents of Pseudopterogorgia species of the Indian ocean

A new ceramide, (2S,3R,4E)-1,3-dihydroxy-2-[(hexadecanoyl)amino]-nonadeca-4-ene (1), cholest-5-en-3β,7β,19-triol (2), identified as its, peracetyl derivative (3), and batyl alcohol (4) were isolated from Pseudopterogorgia species. 1 exhibited antibacterial activity against Gram-positive and Gram-negative bacteria.     

ent-Kaurenoids from the roots of Cacalia pilgeriana

Two new ent-kaurenoids,19-acetoxyl-ent-3β,17-dihydroxykaur-15-ene (1), 19-acetoxyl-ent-3β-hydroxykaur-15-en-17-al (2), together with seven known ent-kaurenoids: ent-kaur-16-en-19-al (3), ent-kaur-16-en-19-oic acid (4), ent-kauran-16β,17-diol (5), ent-15β, 16β-epoxy-17-hydroxykauran-19-oic acid (6),19-acetyl-ent-3β-hydroxyl-kaur-16-ene (7), ent-3β,19-dihydroxykaur-16-ene (8), ent-17-hydroxykaur-15-ene (9), were isolated from Cacalia pilgeriana. Their structures were elucidated by spectroscopic methods including 2D NMR spectral analysis.     

O-methyl nakafuran-8 lactone, a new sesquiterpenoid from a hainan marine sponge Dysidea sp

A new sesquiterpenoid, O-methyl nakafuran-8 lactone (1) has been isolated from a Hainan sponge Dysidea sp. and the structure of the new compound proposed by spectral data, was confirmed by X-ray diffraction analysis. The complete ¹H- and ¹³C-NMR assignments were made on the basis of detailed 2D NMR spectral analysis.

Compound 1 showed strong inhibitory bioactivity against PTP1B with IC₅₀ value of 1.58 μM.     

Triterpenoid Saponins from Leaves and Stems of Panax Quinquefolium L

In the chemical investigation on the saponin composition of leaves and stems of Panax quinquefolium L., two new minor dammarane saponins, quinquenoside L₁ (1) and L₂ (2) have been isolated. By means of physico-chemical evidences and spectral analysis their structures were established as 3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-20-O-β-D-glucopyranosy-dammara-23,25-diene-3β, 12β, 20(S)-triol (1) and 3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-20-O-β-D-D-glucopyranosyl-(24Z)-dammar-24-ene-3β, 12β, 20(S), 26-tetraol (2).     

A new anti-HIV lupane acid from Gleditsia sinensis Lam.

A new lupane acid, 2β-carboxyl,3β-hydroxyl-norlupA (1)-20 (29)-en-28-oic acid (1), together with five known lupane acid derivatives (2-6), were isolated from the stings of Gleditsia sinensis Lam.. Their structures were elucidated on the basis of 1D and 2D NMR techniques. All these known compounds were isolated from this genus for the first time. The new compound 1 showed strong anti-HIV activity.     

A new triterpenoid from Entodon okamurae Broth

One new triterpenoid, entokamurol (1), was isolated from Entodon okamurae Broth, together with other nine compounds, namely dryocrassol (2), chrysophamol (3), physcion (4), 10-nonacosamnol (5), n-hexadecanol (6), phthalic acid isodibutyl ester (7), curcumol (8), β-sitosterol (9) and daucosterol (10). Their structures were elucidated on the basis of extensive NMR (DEPT, DQF-COSY, HMQC, HMBC and NOESY), IR and MS studies. All the compounds were isolated and identified from the genus of Entodon for the first time, and it is also the first report of a guaiane-type sesquiterpenoid and compounds with anthraquinone skeleton in mosses.     

Triterpenoid saponins from Vaccaria segetalis

A new triterpenoid saponin, named segetoside C (1), and two known saponins, vaccaroid A (vaccaroside A) (2) and dianoside G (3), have been isolated from the seeds of Vaccaria segetalis. On the basis of chemical reaction and spectral data, the structure of segetoside C (1) has been established as: gypsogenic acid-28-O-[β-D-glucopyranosyl-(1 → 3)]-[6-O-acetyl-β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranoside.     

Two new diterpenoid dimers,fritillebinide D and E,from bulbs of Fritillaria ebeiensis

Two new ent-kaurane diterpenoid dimers, fritillebinide D (1) and fritillebinide E (2), were isolated from bulbs of Fritillaria ebeiensis G.D. Yu et G.Q. Ji. Their structures have been determined to be ent-3β-acetoxy-kauran-16β, 17-acetal ent-3β-acetoxy-16β-kauran-17(R)-aldehyde (1) and ent-3β-acetoxy-kauran-16β,17-acetal ent-3β-acetoxy-16β-kauran-17(S)-aldehyde (2) by means of spectral analysis.     

Microbial hydroxylation of cinobufagin by Mucor spinosus

Mucor spinosus has been employed for the biotransformation of cinobufagin (1) to afford three metabolites. On the basis of their physico-chemical data, the structures of the transformation products have been characterized as 1β-hydroxy-cinobufagin (2), 12β-hydroxy-cinobufagin (3) and 1β,12β-dihydroxy-cinobufagin (4), of which metabolites 2 and 4 are new compounds. In vitro cytotoxic activities of the biotransformation products and the substrate-cinobufagin have been assayed against four tumor cell lines of Bel 7420, BGC 823, HeLa and HL 60; they all showed cytotoxic activities.     

A new saponin from the leaves and stems of Panax quinquefolium L. collected in Canada

A new dammarane-type saponin named quinquenoside L3 (1) together with vina-ginsenoside R3 (2) were isolated from the leaves and stems of Panax quinquefolium L. collected in Canada. On the basis of physicochemical and spectral evidences, 1 was established as 3-O-β-D-glucopyranosyl-20-O-[β-D-xylopyranosyl-(1 → 6)-β-D-glucopyranosyl] 20(S)-dammar-23-ene-3β, 12β,20,25-tetryol.     

Paeciloxanthone, a new cytotoxic xanthone from the marine mangrove fungus Paecilomyces sp. (Tree1-7)

The metatrophic fungus Paecilomyces sp. (Tree1-7) was isolated from an estuarine mangrove from the Taiwan Strait. The methanol extract of the fungal mycelium exhibited cytotoxicity against hepG2. Paeciloxanthone (1), a new xanthone, and the known compounds emodin (2) and chrysophanol (3), were isolated from the extract. Their structures were elucidated by spectroscopic experiments. Paeciloxanthone (1) exhibited in vitro cytotoxicity against hepG2 (IC₅₀ = 1.08 μg/mL), acetylcholineesterase (AChE) inhibitory (IC₅₀ = 2.25 μg/mL) and antimicrobial activities.     

Selective effects of [D-Ser(O-t-butyl),Leu]enkephalyl-Thr and [D-Ser(O-t-butyl),Leu]enkephalyl-Thr(O-t-butyl), two new enkephalin analogues, on neurotransmitter release and adenylate cyclase in rat brain slices

The selectivity and potency of two new enkephalin-derived δ-opioid receptor agonists, DSTBULET ([D-Ser²(O-t-butyl), Leu⁵]enkephalyl-Thr⁶) and BUBU ([D-Ser²(O-t-butyl),Leu⁵]enkephalyl-Thr⁶(O-t-butyl)) were determined with functional tests in vitro of μ-, δ-, and κ-opioid receptor activation in the rat brain. Both peptides concentration dependently (1 nM-1 μM) inhibited the release of radiolabeled acetylcholine (ACh) from striatal slices (pD₂ 7.6–7.9), an effect exclusively mediated by δ-opioid receptor activation. Fentanyl isothiocyanate (FIT), an irreversible δ-antagonist, completely blocked the inhibitory effects of DSTBULET and BUBU. Up to a concentration of 1 μM, the peptides did not affect striatal [³H]dopamine (DA) release nor cortical [³H]noradrenaline (NA) release, processes which are known to be inhibited by opioids activating κ and μ-receptors, respectively. Furthermore, both DSTBULET and BUBU caused a strong inhibition (pD₂ 8.2–8.3) of D-1 dopamine receptor-stimulated cyclic AMP efflux from striatal slices, an effect known to be mediated by μ- and/or δ-opioid receptor activation. However, the peptides were without effect when D-1 and D-2 dopamine receptors were stimulated simultaneously, a situation in which only μ-agonists are able to inhibit the resulting cAMP efflux. In conclusion, DSTBULET and BUBU appear to display a high selectivity and potency toward functional δ-opioid receptors in the brain.