A sulphated flavone glycoside from Livistona australis and its antioxidant and cytotoxic activity

A new flavone glycoside tricin 7-O-β-glucopyranoside-2″-sulphate sodium salt along with 14 known flavonoid compounds were isolated and identified from the aqueous methanol extract of Livistona australis leaves. Their structures were established on the basis of extensive NMR (1H, 13C, HSQC and H-H COSY) and ESIMS data. Antioxidant and cytotoxicity properties of the methanol extract of the leaves as well as the new compound were investigated.     

Brine shrimp cytotoxicity of Caesalpinia pulcherrima aerial parts, antimicrobial activity and characterisation of isolated active fractions

Caesalpinia pulcherrima Swartz. is an ornamental plant, shrub or a small tree belonging to the family Caesalpiniaceae. The plant has been used for the treatment of inflammatory disorders, skin diseases and so on. In this study, the cytotoxicity of the methanol extract of the aerial parts of C. pulcherrima was tested using an Artemia salina (brine shrimp) bioassay. Further, the methanol extract was fractionated by silica gel column chromatography using a solvent gradient of hexane:ethyl acetate:methanol in different ratios and 56 fractions were collected. On the basis of thin layer chromatography profiles, 13 major fractions were obtained, which were tested for antimicrobial activity against 14 microorganisms using the agar disc diffusion method and also tested for their minimal inhibitory concentration and minimal bactericidal concentration values. In terms of cytotoxicity, the extract caused 26% mortality of brine shrimp larvae after 24?h at a concentration of 1000?μg?mL(-1). Fractions 3, 9 and 10 showed significant antimicrobial activities. Phytochemical analysis of these three fractions led to the identification of 11 compounds, and their structures were established by means of gas chromatography-mass spectroscopy techniques. These findings suggest that these bioactive compounds may be useful as potential antimicrobials. Further investigation is needed to establish the mode of action of these bioactive compounds.     

Antiplasmodial and cytotoxic activities of drimane sesquiterpenes from Canella winterana

The hexane extract from the leaves of Canella winterana exhibited strong activity against the chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10) in vitro (IC50 2.53 microg/mL). Bioassay guided fractionation of this extract has led to the isolation of 5 drimane-type sesquiterpenoids: 9-epideoxymuzigadial, 9-deoxymuzigadial, muzigadial, 3-beta-acetoxypolygodial and the newly isolated hemiacetal, named muzigodiol, with IC50-values of 1.01, 2.19, 0.31, 2.77 and 7.43 microg/mL, respectively. The first four compounds were tested for their cytotoxicity using Chinese Hamster Ovarian (CHO) cells, where they showed IC50-values of 1.82, 33.69, 1.18, and 58.31 microg/mL, respectively. A structure-activity relationship is discussed.     

Cytotoxity of two new coumarin derivatives isolated from Launaea mucronata

The chloroform fraction of methanol (MeOH) extract of the aerial parts of Launaea mucronata was in vitro investigated for cytotoxicity against HCT116, HepG2 and MCF-7 cell lines, and resulted with IC₅₀ = 20.0, 18.6 and 14.30 μg/mL, respectively. The chloroform fraction of the MeOH extract was subjected to further fractionation, which led to the isolation of two new coumarin compounds (6-isobutyl coumarin and 6-isobutyl-7-methyl- coumarin). The structures of the new compounds were elucidated by high field 1D and 2D NMR and ESI-MS spectroscopies. Low polar fractions revealed the isolation of other known triterpene compounds which were identified according to its spectral data and comparison with the literature. New coumarin compounds show high cytotoxicity against MCF-7, HCT116 and HepG2 cell lines.     

A new fatty acid ester of triterpenoid from Celastrus rosthornianus with anti-tumor activitives

The methanol extract of the stalks of Celastrus rosthornianus Loes. afforded a new fatty acid ester of triterpene: 1beta,3beta-dihydroxy-olean-9(11),12-dienyl-3-palmitate (1), and three known compounds beta-amyrin palmitate (2), 3beta-hydroxy-11-oxo-olean-12-enyl-3-palmitate (3) and lupeol palmitate (4). Their structures were established by HRMS, 1D and 2D NMR experiments, as well as, by chemical degradation. The new compound showed cytotoxicity against human cervical squamous carcinoma (Hela) cells.     

Isolation and structure of a monomethylated ganglioside possessing neuritogenic activity from the ovary of the sea urchin Diadema setosum

A new monomethylated ganglioside, DSG-A (3), was obtained, together with four known gangliosides, compounds (1, 2, 4, 5), from the lipid fraction of the chloroform/methanol extract of the ovary of the sea urchin Diadema setosum. The structures of the new ganglioside was determined on the basis of chemical and spectroscopic evidence to be 1-O-[9-O-methyl-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moiety of 3 was composed of C18-phytosphingosine base, and 2-hydroxy and nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor, in which compound 3 showed the most potent activity.     

Isolation and characterisation of novel antioxidant constituents of Croton zambesicus leaf extract

A 1,1-diphenyl-2-picrylhydrazyl (DPPH)-activity-directed fractionation was used to target antioxidant constituents of the ethyl acetate fraction obtained from a 20% aqueous methanol crude extract of Croton zambesicus leaf. Repeated column chromatography of the fraction on silica gel and Sephadex LH-20 led to the isolation of a new natural product, identified as quercetin-3-O-β-6″(p-coumaroyl) glucopyranoside-3'-methyl ether, helichrysoside-3'-methyl ether (1), along with kaempferol-3-O-β-6″(p-coumaroyl) glucopyranoside, tiliroside (2) and apigenin-6-C-glucoside, isovitexin (3) as the antioxidant constituents. The structures of the isolated compounds were elucidated using spectroscopic techniques, namely NMR (1D and 2D) and mass spectrometry. Compounds 1 and 2 are reported from this species for the first time. In the qualitative antioxidant assay, the three isolated compounds instantly bleached the DPPH (0.2% MeOH) purple colour indicating antioxidant activity. In the quantitative antioxidant assay, all the isolated compounds demonstrated weak antioxidant activity compared to quercetin and rutin used as positive control antioxidant agents. The compounds displayed little to no cytotoxicity against Vero cells in an in?vitro assay. The presence of these antioxidant compounds in the leaf extract of C. zambesicus could provide a rationale for the ethnomedicinal use of the plant in the management of oxidative-stress-related diseases in folk medicine.     

Cytotoxic limonoids from Brazilian Melia azedarach

Three new C-seco limonoids (1-3) and one new tetracyclic limonoid (4) were isolated from a methanol extract of the ripe fruits of Melia azedarach collected in Curitiba, Brazil, and their structures were elucidated by spectroscopic data analysis and comparison of spectral data with those of the previously known compounds. Among the limonoids isolated in the present study, compounds 3 and 4 exhibited significant inhibitory activity against HeLa S3 cancer cells, whereas 1 and 2 showed weak cytotoxicity.     

A new cytotoxic and tubulin-interactive milnamide derivative from a marine sponge Cymbastela sp

[structure: see text] The crude methanol extract of a marine sponge Cymbastela sp. collected in Papua New Guinea was selected for chemical investigation due to its significant cytotoxicity. Fractionation of the extract led to the isolation of jaspamide (1), hemiasterlin (2), milnamide A (3), and a new metabolite, milnamide D (4). The structure was solved by interpretation of NMR and mass spectra data. The cytotoxic and antitubulin activities of milnamide D (4) were evaluated.     

A new cytotoxic limonoid from Odontadenia macrantha from the Suriname rainforest

Bioassay‐guided fractionation of the methanol extract of Odontadenia macrantha afforded a new limonoid, odontadenin A (1) and two known triterpenoids, lupeol (2) and α‐amyrin (3). The structure of 1 was established on the basis of 1D and 2D NMR and high‐resolution fast atom bombardment mass spectrometric data. The new compound was found to possess moderate cytotoxicity against A2780, the ovarian cancer cell line. Copyright © 2003 John Wiley & Sons, Ltd.     

A phenyldilactone,bisnorsesquiterpene, and cytotoxic phenolics from Maytenus senegalensis leaves

Maytenus senegalensis Lam. (Celastraceae) leaves are traditionally used in West Africa for the management of cancer and other disorders associated with inflammation. In this study, bioactivity-guided fractionation of the methanol leaf extract of Maytenus senegalensis led to the isolation of 11 compounds, including the new phenyldilactone, maysedilactone (1). All isolated compounds were tested for cytotoxicity against mouse lymphoma cell line (L5178Y). Only (−) epigallocathechin showed high cytotoxicity and completely inhibited cell growth at the investigated dose of 10 μg/mL. This result supports the claimed efficacy of Maytenus senegalensis leaf extract in ethnomedicinal treatment of cancer.     

A new sesquiterpene from hairy root culture of Artemisia annua

<正>A new sesquiterpene(Z)-7-acetoxy-methyl-11-methyl-3-methylenedodeca-1,6,10-triene(AMDT) was isolnted and identified from the methanol extract of the hairy root culture of Artemisia annua.The structure of AMDT was determined based on the analysis of spectroscopic data,notably of the 2D NMR spectra.This new compound showed cytotoxicity against human tumor cell lines 95-D and HeLa with IC_(50) values of 27.08 and 20.12μmol/L,respectively.     

Separation of triterpenoid saponins from the root of Bupleurum falcatum by counter current chromatography: The relationship between the partition coefficients and solvent system composition

A separation method using counter current chromatography coupled with an evaporative light‐scattering detection system was developed to purify five triterpenoid saponins from the roots of Bupleurum falcatum. The methanol extract was loaded onto a Diaion® HP20 column and fractionated by a methanol and water gradient elution. The saikosaponin‐enriched fraction was obtained by elution with 100% methanol. The two‐phase solvent systems used for separation were composed of chloroform/methanol/isopropanol/water at a volume ratio of 60:60:1:60 and 6:6:1:6. The relationship between the isopropanol ratio of each phase and the partition coefficients of the target compounds was investigated by calculating partition coefficient by high‐performance liquid chromatography and measuring the accurate composition of each phase by ¹H NMR spectroscopy. Each fraction obtained was collected and dried, which yielded the following five saikosaponins from 700 mg of injected sample: saikosaponin B₁ (8.7 mg), saikosaponin A (86 mg), saikosaponin B₃ (17 mg), saikosaponin B₂ (41 mg), and saikosaponin C (33 mg). Saikosaponin A showed the most potent cytotoxicity against human cancer cells (gastric cancer, AGS cells; breast cancer, MCF‐7 cells; and hepatoma, HepG2 cells) after 24 h. The IC₅₀ values for the above three cell types were 34.6, 33.3, and 23.4 μmol/L, respectively.     

Isolation and identification of a new neo-clerodane diterpenoid from Teucrium chamaedrys L.

Teucrium chamaedrys L. is an aromatic and medicinal plant used as traditional medicine. Aerial parts of the plant material were dried and extracted with hexane–dichloromethane (extract 1), ethyl acetate–dichloromethane (extract 2) and methanol–dichloromethane (extract 3) in a ratio of 1:1 at rt successively. The solvents were evaporated to give crude extracts. Extract 1 was suspended in water at 60°C then partitioned successively with hexane and ethyl acetate to give hexane and ethyl acetate portions. After the column chromatography (silica gel) of ethyl acetate extract, one new and four known compounds were isolated. The new compound was named as 1(12S,18R)-15,16-epoxy-2β,6β-dihydroxy-neo-cleroda-13(16),14-dien-20,l2-olide-l8,l9-hemiacetal (teuchamaedryn D) (4). The known compounds were teucrin A (1), dihydroteugin (2), teucroxide (3), syspirensin A (5). The chromatographic methods were also applied for extract 3 to isolate verbascoside (6) and teucrioside (7). The structure of isolated compounds was elucidated by spectroscopic methods including LC-TOF/MS, 1D NMR and 2D NMR.     

New hedgehog/GLI-signaling inhibitors from Adenium obesum

The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. We recently constructed a cell-based screening system to search for Hh/GLI signaling inhibitors from natural resources. Using our screening system, Adenium obesum was found to include Hh/GLI signaling inhibitors from our tropical plant extract libraries. Bioassay-guided fractionation of this plant extract led to the isolation of 17 cardiac glycosides (1-17), including 3 new compounds (4, 9, 16). These compounds showed strong inhibitory activities, especially the IC(50) of 17 is 0.11 μM. The inhibition of GLI-related protein expression with 3, 9, 11, 15 and 17 was observed in human pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited. These compounds also showed selective cytotoxicity against two cancer cell lines, with less effect against normal cells (C3H10T1/2). RT-PCT examinations showed that Ptch mRNA expression by 3, 11, 15 and 17 was inhibited.     

Constituents of Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory activity

A new sesquiterpene 2,9-humuladien-6-ol-8-one (1) was isolated from methanol extract of Zingiber aromaticum, along with 15 known compounds. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses. The isolated compounds were tested for their inhibitory activity on the metabolism mediated by cytochrome P450 3A4 (CYP3A4) and CYP2D6.     

Methyl quadrangularates A-D and related triterpenes from Combretum quadrangulare

From the MeOH extract of leaves of Combretum quadrangulare, fifteen new cycloartane-type triterpenes, methyl quadrangularates A-D (1-4) and N-P (8, 6, 12), methyl 24-epiquadrangularate C (5), quadrangularic acid E (9), 23-deoxojessic acid (10), 1-O-acetyl-23-deoxojessic acid (11), quadragularols A (7) and B (13) and norquadrangularic acids B (14) and C (15) were isolated together with two known cycloartane-type triterpenes, methyl 23-deoxojessate (16) and 4beta,14alpha-dimethyl-5alpha-ergosta-9beta++ +,19-cyclo-24(31)-en-3beta-hydroxy-4alpha-carboxylic acid (17). Betulinic acid (18), beta-sitosterol (19), kamatakenin (20), isokaempferide (21), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (22) and 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (23) were also obtained from the same extract. The structures of the new compounds were elucidated on the basis of spectral analysis and chemical conversions. All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the cycloartane-type triterpenes showed various degrees of cytotoxicity, whereas all the flavonoids possessed strong cytotoxicity with ED50 values equal to or less than 6 microM.     

Phenolic compounds from Eucalyptus gomphocephala with potential cytotoxic and antioxidant activities

Two new phenolic compounds, 2,4,6-trihydroxy-5-methyl-acetophenone 2-O-beta-D-glucopyranoside (3), and benzyl alcohol 7-O-(3',4',6'-tri-O-galloyl)-beta-D-glucopyranoside (8), together with eight known phenolic compounds, were isolated from the 70% aqueous acetone extract of Eucalyptus gomphocephala DC. (Myrtaceae). The isolated compounds were elucidated based on their 1H, 13C, DQF-COSY, selective 1D-TOCSY, HSQC, and HMBC NMR spectroscopic and ESI-MS data. The antioxidant effect of the phenolic compounds was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical and super oxide anion radical scavenging assays. The cytotoxicity of the isolated compounds was evaluated using HeLa cell line.     

Isolation and characterisation of new bio-active compounds from Euphorbia cornigera: cytotoxic ingenol esters

The aerial parts of Euphorbia cornigera Boiss., on extraction with MeOH, yielded new bio-active constituents (1, 2) and known compounds (3 and 4) after MTT cytotoxicity assay-guided fractionation and chromatographic separation were conducted. From the aerial parts of E. cornigera Boiss., new bio-active constituents were extracted in methanol. The extract was partitioned in different organic solvents and the ethylacetate-soluble portion was subjected to Craig's distribution. The MTT cytotoxicity assay-guided chromatographic separation yielded four (1-4), out of which two (1, 2) were new and two known (3, 4) bio-active compounds, and they are reported for the first time from this source. Their structure and relative stereochemistry were established by analysing spectroscopic and mass measurement data. The isolates were named as: 13-O-[(2Z ,4 E ,6 Z)]-deca-2,4,6-trienoylingenol (1), 13-O-( 2 Z ,4 E ,6 Z)-deca-2,4,6-trienoyl-20-O-angeloylingenol (2), 13-O-dodecanoyl-20-O-hexanoylingenol (3) and 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoyl-20-O-hexadecanoylingenol (4). Literature revealed that compounds 1 and 2 are new metabolites, while 3 and 4 are known, and are reported for the first time from this source. Cytotoxicities of isolates were evaluated in terms of IC(50) against RAW and HT-29 cell lines through MTT assay using ambrucin hydrochloride as a control. Compound 3 showed more activity than control, while 1, 2 and 4 were moderate.     

Anti-plasmodial and cholinesterase inhibiting activities of some constituents of Psorospermum glaberrimum

Glaberianthrone (1), a new bianthrone was isolated from the hexane extract of the stem bark of Psorospermum glaberrimum together with thirteen known compounds: 3-geranyloxyemodin anthrone (2), friedelan-3-one (3), 3-prenyloxyemodin anthrone (4), 3-geranyloxyemodin (5), 3-prenyloxyemodin (6), friedelan-3-ol (7), acetylvismione D (8), betulinic acid (9), 2-geranylemodin (10), bianthrone A2b (11), bianthrone 1a (12), emodin (13) and 2-prenylemodin (14). The structures of the isolated compounds were established by means of spectroscopic methods. The extracts and the isolated compounds were tested in vitro for their anti-plasmodial activity against Plasmodium falciparum (chloroquine resistant strain W2) and for their acetyl- and butyrylcholinesterase inhibitory properties. The n-hexane extract showed good anti-plasmodial activity against P. falciparum W2 strain, with IC(50) of 0.87 microg/ml. It also exhibited 65.5% and 98.2% of acetyl- and butyrylcholinesterase inhibition at 0.2 mg/ml, respectively. Compounds 2 and 8 showed the best potencies against P. falciparum W2 strain with IC(50) of 1.68 microM and 0.12 microM, (0.66 microg/ml and 0.054 microg/ml) respectively. All tested compounds showed good butyrylcholinesterase inhibition activities with compound 12 displaying the best potency (IC(50) 9.25+/-0.25 microM). All the tested compounds showed weak inhibitory activity against acetylcholinesterase.