Xanthone derivatives from the fermentation products of an endophytic fungus Phomopsis sp.

Three new xanthones, 1,5-dihydroxy-3-hydroxyethyl-6-methoxycarbonylxanthone (1), 1-hydroxy-5- methoxy-3-hydroxyethyl-6-methoxycarbonylxanthone (2), and 1-hydroxy-3-hydroxyethyl- 8-ethoxycarbonylxanthone (3), along with seven known xanthones (4–10) were isolated from the fermentation products of an endophytic fungus Phomopsis sp.. Their structures were elucidated by spectroscopic methods including extensive 1D- and 2D-NMR techniques. Compounds 1–10 were also tested for their cytotoxicity against five human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) by MTT method using paclitaxel as positive control. Compounds 1 and 3 showed cytotoxicity against A549 cell lines with IC50 values of 3.6 and 2.5 μM, respectively. In addition, 1 was cytotoxic to MCF7 cells with IC50 value of 2.7 μM.     

Echinosporins as new cell cycle inhibitors and apoptosis inducers from marine-derived Streptomyces albogriseolus

Bioassay-guided fractionation of the ethyl acetate extract from the fermentation broth of marine-derived Streptomyces albogriseolus A2002 led to the isolation of echinosporin (1) and 7-deoxyechinosporin (2). Compound 1 inhibited the proliferation of tsFT210, K562 and HCT-15 cancer cells (IC(50) 91.5 microM, 25.1 microM and 247 microM respectively) and 2 showed the same effect on K562 cells (IC(50) 143 microM). Flow cytometric analysis suggested that 1 and 2 exert their anti-proliferative effects on those cells through inhibiting cell cycle at the G(2)/M phase and inducing apoptosis.     

Flavonoids with antiplasmodial and cytotoxic activities of Macaranga triloba

A new flavanone derivative, malaysianone A (1), four prenylated flavanones, 6-prenyl-3'-methoxyeriodictyol (2), nymphaeol B (3), nymphaeol C (4) and 6-farnesyl-3',4',5,7-tetrahydroxyflavanone (5), and two coumarins, 5,7-dihydroxycoumarin (6) and scopoletin (7), were isolated from the dichloromethane extract of the inflorescences of Macaranga triloba. The structures of these compounds were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR and mass spectrometry. The cytotoxic activity of the compounds was tested against several cell lines, with 5 inhibiting very strongly the growth of HeLa and HL-60 cells (IC(50): 1.3 μg/ml and 3.3 μg/ml, respectively). Compound 5 also showed strong antiplasmodial activity (IC(50): 0.06 μM).     

Cytotoxic sesquiterpenes and lignans from Saussurea deltoidea

Two new sesquiterpenes deltoiden A (1) and deltoiden B (2), and two new lignans deltoignan A (9) and deltoignan B (10), together with 14 known compounds, including six sesquiterpenes 3-8 and three lignans 11-13, were isolated from the whole plant of Saussurea deltoidea. Compounds 3-8 and 11-17 were isolated for the first time from this plant. Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities of compounds 1-13 were tested against three cancer cell lines A549, Hela and SMMC-7721. Results showed that 5, 6 and 7 exhibited cytotoxicity against SMMC-7721 with the IC(50) values of 6.49, 9.53, 1.23 μg/ml, 5 and 7 against A549 with the IC(50) values of 4.99 and 5.35 μg/ml, 5, 6, 7, 13 against Hela with the IC(50) values of 1.40, 4.75, 0.93 and 5.42 μg/ml, respectively. The structure-activity relationships of sesquiterpenes 1-8 were discussed on the base of cytotoxic results.     

A cytotoxic 4α-methyl steroid from the aerial parts of Cimicifuga foetida L

A new 4α-methyl sterol, cimisterol A (1), together with five known compounds (2-6), were isolated from the aerial parts of Cimicifuga foetida L. The new compound's structure was determined with the help of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited broad-spectrum and potent cytotoxic activities against human HL-60, Jurkat, K562, U937, HepG-2, and SGC-7091 cell lines, with IC(50) values of 7.23, 2.89, 6.88, 3.38, 4.21, and 4.89 μM, respectively. Compound 3 showed moderate to weak activities to all cell lines, except for SGC-7091, having IC(50) values ranging from 13.37 to 17.72 μM. This is the first time a cytotoxic 4α-methyl sterol constituent was discovered from Cimicifuga spp.     

Amides with anti-platelet aggregation activity from Piper taiwanense

Three new amides, taiwanamides A-C (1-3), and two known amides, 1-cinnamoylpyrrolidine (4) and 1-(m-methoxycinnamoyl)pyrrolide (5), have been isolated from the stem of Piper taiwanense. The structures of the new amides were determined by spectral analyses. These five amides exhibited inhibitory activity of platelet aggregation in vitro. Taiwanamide C (3) owned the most potent inhibition activity of platelet aggregation induced by collagen showing IC(50) value as 8.9 microM. Taiwanamide B (2) and 1-(m-methoxycinnamoyl)pyrrolide (5) exhibited IC(50) values of 17.3 and 17.4 microM, respectively.     

Anticancer activities of two sesquiterpene lactones, millerenolide and thieleanin isolated from Viguiera sylvatica and Decachaeta thieleana

The present study was carried out in order to examine the anticancer properties of two sesquiterpene lactones, millerenolide and thieleanin, isolated from Viguiera sylvatica and Decachaeta thieleana, against cell lines in vitro, and on the growth B16/BL6 melanoma tumors in C57BL/6 mice. Millerenolide and thieleanin showed a similar pattern of cytotoxicity with the greatest effect on viability being evident with A549 human lung cancer cells (IC(50) - 40 and 32 microM respectively), and with the 3T3/HER2 cell line which are 3T3 mouse fibroblasts transfected with the HER2 oncogene (IC(50) - 16 and 28 microM respectively). The parent 3T3 cells and the B16/BL6 mouse melanoma cells were less sensitive to these compounds, with thieleanin showing an IC(50) with B16/BL6 greater than the highest dose tested (203 microM). Treatment with millerenolide (8 mg/kg, i.p. on days 0, 2 and 4 post-inoculation) significantly inhibited the growth of subcutaneous B16/BL6 tumors in C57BL/6 mice, (50% inhibition at day 25, P=0.015), as well as retarding the appearance of detectable tumor (millerenolide - day 15.2+/-0.4 vs control - day 12.8+/-0.5, mean+/-SEM, P=0.011). In contrast, treatment with thieleanin (8 mg/kg every other day up to the day of kill) neither retarded the appearance of the tumor nor its growth.     

Five new furostanol saponins from the rhizomes of Tupistra chinensis

Five new furostanol saponins (1-5), together with three known compounds (6-8) were obtained from the n-butanol soluble fraction of ethanol extract from Tupistra chinensis. Their structures were determined on the basis of chemical methods and spectral data. The isolated compounds were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, compounds 6, 7, and 8 showed cytotoxicity against A549 cancer cell lines with IC(50) values of 6.6, 6.7 and 29.1 μM, respectively.     

Cytotoxic ellagitannins from Reaumuria vermiculata

Three ellagitannins and one disulfated flavonol were isolated from the aerial parts of Reaumuria vermiculata L. Besides that, 16 known compounds were characterized as well. The structures of all compounds were elucidated on the basis of spectroscopic data including 1D and 2D NMR and ESI HR-FTMS. The in vivo antioxidant activity using the oxygen radical absorbance capacity (ORAC) method, of the extract, its column fractions and two of the isolated ellagitannins was accomplished. In addition, a possible cytotoxicity of the extract and two of the new ellagitannins on HaCaT human keratinocytes and the activity of both compounds against the prostate cancer cell line (PC-3) were also assessed, whereby a potent cytotoxicity with IC(50) less than 1μg/ml was determined for both compounds. Besides, the extract exhibited a potential cytotoxic effect against four different solid tumor cell lines, namely liver (Huh-7), colorectal (HCT-116), breast (MCF-7) and prostate (PC-3). The IC(50)s were found to be substantially low (ranged from 1.3±0.15 to 2.4±0.22μg/ml) with relatively low resistance possibility reaching to 0% in the case of Huh-7 cell.     

Amoebicidal and giardicidal compounds from the leaves of Zanthoxylum liebmannianun

The crude ethanol extract from the leaves of Zanthoxylum liebmannianum exhibited inhibitory effect on the reproduction of trophozoites of Entamoeba histolytica (IC(50)=3.48 microg/ml) and Giardia lamblia (IC(50)=58.00 microg/ml). From this extract, asarinin, hyperin, beta-sitosterol, and beta-sitosterol glucoside were isolated. Among them, asarinin was the most active with IC(50) values of 19.86 microg/ml for E. histolytica and 35.45 microg/ml for G. lamblia. The remaining compounds showed moderate activity against both parasites.     

Antineoplastic activity of selected constituents of Duguetia glabriuscula

The cytotoxic effects of seven constituents isolated from Duguetia glabriuscula were evaluated against Hep2 human larynx carcinoma cells. The cytotoxicity exhibited by beta-sitosterol was as strong as that of cis-platin. (+)-Alloaromadendran-10,14beta-diol caused inhibition of cellular growth with IC50 values lower than 25 microg/ml, a feature that was considered as revealing significant activity. Polycarpol showed borderline cytotoxicity, whereas the other compounds were inactive.     

Steroids with inhibitory activity against the prostate cancer cells and chemical diversity of marine alga Tydemania expeditionis

A new diketosteroid, (E)-stigmasta-24(28)-en-3,6-dione (1), along with three known steroids (2-4) was isolated from marine alga Tydemania expeditionis collected in China Sea. Their structures were elucidated by extensive spectroscopic methods. Comparison of the chemical constituents revealed significant diversity among different locations. The biological activities of 1, 3 and 4 were evaluated on the prostate cancer cell lines and androgen receptor. Compound 1 exhibited moderate inhibitory activities against the prostate cancer cells DU145, PC3 and LNCaP with IC(50) values of 31.27±1.50, 40.59±3.10 and 19.80±3.84 μM, respectively. Compound 3 showed more potent activities with IC(50) values of 12.38±2.47, 2.14±0.33 and 1.38±0.07 μM, respectively. However, compound 4 showed only weak inhibitory activities on LNCaP cells and was inactive on DU145 and PC3 cells. A competitive binding assay showed that compound 1 exhibited significant affinity to the androgen receptor with an IC(50) value of 7.19±0.45 μM, while 3 and 4 were inactive. The fact that the inhibitory properties of 1 and 3 against the prostate cancer cells were inconsistent with their affinities to the androgen receptor suggested that there might be other mechanism of action involved in the cytotoxic activity.     

A new flavonoid glycoside from the leaf of Cephalotaxus koreana

A new flavone glycoside, apigenin 5-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside (1), along with four known flavonol glycosides (2-5), were isolated from the leaf of Cephalotaxus koreana. The new glycoside 1 showed inhibitory activity in superoxide radical scavenging assay with IC(50) value of 13.0 microM, while it showed weak activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. Compounds 2-5 exhibited antioxidant activity in scavenging DPPH and superoxide radicals with IC(50) values ranging from 5.7 to 22.3 microM.     

An unusual taxodione derivative from hairy roots of Salvia austriaca

From a root culture of Salvia austriaca, transformed with Agrobacterium rhizogenes, a new diterpenoid was isolated and its chemical structure was determined as 7-(2-oxohexyl)-11-hydroxy-6, 12-dioxo-7,9(11),13- abietatriene [= 7-(2-oxohexyl)-taxodione] on the basis of spectroscopic methods, especially 1D and 2D NMR, and by comparison with structurally related compounds. This compound represents a hitherto unknown 2-oxohexyl diterpenoid derivative. Cytotoxic studies revealed that the new compound exhibited high cytotoxic activity against three cancer cell lines with IC(50) values ranging from 0.63 to 0.72μM. Its cytotoxic effectiveness against the cancer cells was ten fold higher than that of taxodione.     

Cytotoxic triterpene saponins from the leaves of Aralia elata

Phytochemical investigation of the leaves of Aralia elata has led to the isolation of four new compounds, 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl oleanolic acid (1), 3-O-[β-D-glucopyranosyl (1→3)-β-D-glucopyranosyl (1→3)]-[β-D-glucopyranosyl (1→2)]-β-d-glucopyranosyl hederagenin 28-O-β-D-glucopyranoside (2), 3-O-{[β-D-glucopyranosyl (1→2)]-[β-d-glucopyranosyl (1→3)-β-d-glucopyranosyl (1→3)]-β-D-glucopyranosyl} oleanolic acid 28-O-β-D-glucopyranosyl ester (3) and 3-O-[β-D-glucopyranosyl (1→2)]-[β-D-glucopyranosyl (1→3)]-β-d-glucopyranosyl caulophyllogenin (4) and two known compounds, 3-O-[β-D-glucopyranosyl (1→3)-α-l-arabinopyranosyl]-echinocystic acid (5) and 3-O-α-L-arabinopyranosyl echinocystic acid (6). The structural determination was accomplished with spectroscopic analysis, in particular (13)C-NMR, 2D-NMR and HR-ESI-MS techniques. Compounds 1-6 were tested for their inhibition of the growth of HL60, A549 and DU145 cancer cells. Compound 1 showed significant cytotoxic activity against HL60 and A549 cancer cells with IC(50) values of 6.99μM and 7.93μM respectively. In addition, compounds 5 and 6 showed significant cytotoxic activity against HL60 cancer cells with IC(50) values of 5.75μM and 7.51μM, respectively.     

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitory effect of Vitis vinifera

Activity-guided fractionation of the methanol extract of Vitis vinifera bark led to the isolation of epsilon-viniferin, ampelopcin A, vitisin A and vitisin B. Vitisin A and vitisin B showed a remarkable inhibitory activity against 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase with IC50 value of 42.1 microM and 23.9 microM, respectively.     

Cytotoxic activity screening of some indigenous Thai plants

The 50% ethanolic extracts from 14 plant species used in Thai traditional folklore were screened for cytotoxic activity against a malignant human hepatoma (HepG2) cell line and a normal African green monkey kidney (Vero) cell line. The extracts of Polyalthia evecta and Erythroxylum cuneatum showed potent anticancer activity in the HepG2 cell line with IC(50) of 70+/-3 microg/ml and 64+/-4 microg/ml, respectively. P. evecta demonstrated more selectivity to the HepG2 than the Vero cell (selectivity index>14.3) indicating its potential for biopharmaceutical use.     

New cytotoxic quinolone alkaloids from fruits of Evodia rutaecarpa

Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1-methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these compounds were determined by spectroscopic analyses. The cytotoxic activities of all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and Hep G(2) cells were evaluated by MTT assay. The results showed that these alkaloids inhibited cell proliferation with IC(50) values between 14μM and 22μM.     

Preliminary antiproliferative effects of some species of Terminalia, Combretum and Pteleopsis collected in Tanzania on some human cancer cell lines

Methanolic extracts (25 microug/ml) of species belonging to the genera of Combretum, Terminalia and Pteleopsis, collected during a field expedition in Tanzania in 1999, were screened for their antiproliferative and cytotoxic effects against three human cancer cell lines (HeLa, cervical carcinoma; T 24, bladder carcinoma; and MCF 7, breast carcinoma). A leaf extract of Combretum fragrans and a fruit extract of C. zeyheri gave the strongest antiproliferative and cytotoxic effects of all the twenty-four extracts screened in this investigation. In contrast to the highly powerful leaf extract of C. fragrans, the root extract of this species gave no cytotoxic effects against the investigated cancer cell lines at a concentration of 25 microg/ml. The other investigated species of Combretum and Terminalia differed greatly in their cytotoxic potential. Root extracts of Terminalia sambesiaca and T. sericea gave the strongest cytotoxic effects of the five species of Terminalia used in this study. Eight of the twenty-four investigated plant extracts showed pronounced cytotoxic effects (<30% proliferation compared to the control) against the T 24 bladder cancer cells, seven against the HeLa cells and four against the MCF 7 cells.     

A new cytotoxic guaianolide from Chrysanthemum boreale

A new cytotoxic guaianolide was isolated from Chrysanthemum boreale Makino. The structure of guaianolide was elucidated as 8-acetoxy-4,10-dihydroxy-2,11(13)-guaiadiene-12,6-olide (1). Compound 1 exhibited cytotoxic activity (IC(50)< or =4 microg/ml) against all five human cancer cell lines tested.