New cytotoxic sesquiterpene lactones from Anthemis scrobicularis

Four new sesquiterpene lactones, 4α-hydroxy-guaia-10(14),11(13)-diene-12,6α-olide (1), 4α-hydroxy-9α-acetoxy-guaia-1(10),2-diene-12,6α-olide (4), 4α-hydroxy-9β-acetoxy-guaia-1(10),2-diene-12,6α-olide (5), and 1α,4α-dihydroxy-9α-acetoxy-guaia-10(14),2-diene-12,6α-olide (6), were isolated from the aerial parts of Anthemis scrobicularis. Their structures were elucidated on the basis of their IR, NMR, and MS spectroscopic data. In addition, two known sesquiterpene lactones micheliolide (2) and achillin (3) were also isolated. The cytotoxicity of some of the isolated compounds was tested against HCT 116, HepG-2, and MCF-7 cell lines. Micheliolide and 4α-hydroxy-guaia-10(14),11(13)-diene-12,6α-olide showed pronounced inhibitory activity while 4α-hydroxy-9α-acetoxy-guaia-1(10),2-diene-12,6α-olide showed weak activity.     

Two new sesquiterpene lactone glycosides from Artemisia frigida Willd.

The investigation of EtOAc-soluble fraction from the aerial parts of Artemisia frigida has led to the isolation of two new sesquiterpene lactone glycosides, named as artemofriginoside A and artemofriginoside B. Their structures were characterized as 3β-(β-d-glucopyranosyloxy)-8β-(p-hydroxyphenylacetyloxy)-4(15),10(14),11(13)-guaiatrien-1α,5β,6β,7αH-12,6-olide (1) and β-(β-d-glucopyranosyloxy)-8β-(2-hydroxy-3-methylbutanoyloxy)-4(15),10(14),11(13)-guaiatrien-1α,5β,6β,7αH-12,6-olide (2), on the basis of 1D and 2D NMR spectral analysis.     

Cytotoxic effects of sesquiterpene lactones from the flowers of<Emphasis Type="Italic">Hemisteptia lyrata</Emphasis> B

Four guaia-12,6-olide type sesquiterpene lactones, aguerin B (1), 8alpha-acetoxyzaluzanin C (2), cynaropicrin (3), and deacylcynaropicrin (4), were isolated from the flowers of Hemisteptia lyrata Bunge. It is the first report on the isolation of compounds 1-4 from Hemisteptia species. All the isolates (1-4) were examined for their cytotoxic activity against SK-OV-3, LOX-IMVI, A549, MCF-7, PC-3, and HCT-15 human cancer cell lines.     

New cytotoxic sesquiterpene lactones from Warionia saharae

Cytotoxicity-guided fractionation of the methanol soluble part of the dichloromethane extract of the leaves of Warionia saharae led to the isolation of the two new guaianolide-type sesquiterpene lactones, 5 alpha H-3 beta,4 beta-epoxy-14-oxo-guaia-1(10),11(13)-dien-6 alpha,12-olide (1), 5 alpha H-2 beta,4 beta-epoxy-3 alpha-hydroxy-guaia-1(10),11(13)-dien-6 alpha,12-olide (6), and the new eudesmane type sesquiterpene 1 beta,6 alpha-dihydroxycostic acid ( 4). In addition, the known sesquiterpene lactones 5 alpha H-2 beta-hydroxyguaia-3(4),10(14),11(13)-trien-6 alpha,12-olide (2), reynosin (3), 5 alpha H-1 alpha,10 alpha:3 alpha,4 alpha-diepoxyguaia-11(13)-en-6 alpha,12-olide (5), and dehydroleucodin (7) were isolated together with the known flavone hispidulin. Cytotoxicity testing of the sesquiterpene lactones against the KB cancer cell line (ATCC CCL17) revealed IC50 values of 3.5 (1), 2.6 ( 2), 2.7 ( 3), 4.3 ( 5), 3.6 ( 6), and 1.3 (7) microg/mL. Compound 4 was not active up to 20 microg/mL.     

A new inositol derivative from Prenanthes macrophylla

A new chiro-inositol ester, 4-hydroxyphenylacetyl-3-d-chiro-inositol ester (1), was isolated from the whole plants of Prenanthes macrophylla Franch., along with 10 known compounds, 4-hydroxyphenylacetic acid (2), trans-ethyl caffeate (3), cis-ethyl caffeate (4), protocatechualdehyde (5), luteolin (6), luteolin-7-O-β-d-glucoside (7), 15-hydroxy-2-oxo-guai-3-en-1α,5α,6β,7α,10α,11βH-12,6-olide (8), 15-glucopyranosyloxy-2-oxo-guaia-3,11(13)-dien-1α,5α,6β,7α,10αH-12,6-olide (9), ursolic acid (10), and oleanolic acid (11). Their structures were elucidated on the basis of spectroscopic analyses including HR-ESI-MS, ESI-MS, (1)H and (13)C NMR, HSQC, HMBC, and ROESY, and chemical evidences.     

Sesquiterpene lactones from Inula hookeri

Four new sesquiterpene lactones, (1 S,5 R,6 S,7 S,8 R,9 R,10 S,11 S)-6-acetoxy-9-hydroxy-4-oxo-pseudoguai-2(3)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-ethoxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-hydroxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, and 14-acetoxy-1 β,5 α,7 αH-4 β-hydroxy-guai-9(10),11(13)-dien-12,8 α-olide, along with 26 known sesquiterpene lactones, were isolated from the whole plants of Inula hookeri C. B. Clarke. Their structures were established based on spectroscopic methods including HRESIMS, 1D and 2D NMR, and CD techniques. All compounds were evaluated for their cytotoxic activities against HepG2, HeLa, PC-3, and MGC-803 cell lines by CCK-8 assay. Some of the isolates, especiallly pseudoguaianolides and guaianolides, exhibited significant cytotoxicities against these four examined cell lines.     

The constituents ofTaraxacum hallaisanensis roots

Three sesquiterpene lactone compounds, two novel(1β, 3β-dihydroxy-6β, 11β, 4α, 5α, 7αH-eudesm-12,6-olide-1-O-β-D-glucopyranoside, 1β, 3β-dihydroxy-6β, 4β, 5α, 7αH-eudesm-11 en-12,6-olide-1-O-β-D-glucopyranoside) and 1β, 3β-dihydroxy-6β, 11β, 4α, 5α, 7αH-eudesm-12,6-olide were isolated from the aqueous fraction of MeOH extract of the roots fromTaraxacum hallaisanensis (Compositae) employing Amberlite XAD-2, ODS-gel, silica gel and Sephadex LH-20 column chromatographics. Another known compound, (?)-epicatechin, was isolated from the aqueous fraction of the MeOH extract. The total MeOH extract also contained phytosterol and a mixture of β-amyrin acetate, α-amyrin acetate and lupeol acetate. Structures of isolated compounds were elucidated by spectroscopic parameters of IR, Mass,¹³C-NMR,¹H-NMR,¹H-¹H COSY,¹³C-¹H COSY and HMBC.     

Two new eudesmanolides from Inula racemosa

Two new eudesmane-type sesquiterpene lactones were isolated from the roots of Inula racemosa and their structures were elucidated as 3β-hydroxy-11α,13-dihydroalantolactone (1) and 11α-hydroxy-eudesm-5-en-8β,12-olide (2). Their cytotoxic activities against five human cancer cell lines had been tested and compound 2 exhibited weak cytotoxic activity against BEL-7402 and HCT-8 cell lines. The anti-inflammatory activities were also tested, but neither of them showed any activities.     

New guaiane sesquiterpene lactones from Ixeris dentata

Three new guaiane-type sesquiterpene lactones (1-3), together with nine related sesquiterpenes (4-12), were isolated from the whole extract of Ixeris dentata (Asteraceae). The chemical structures of isolates 1-12 were established by spectroscopic analyses as 3 β,8 β-dihydroxy-guaia-10(14)-en-1 α,4 α,5 α,6 β,7 α,11 βH-12,6 α-olide (1), ixerin N 6'- O-acetate (2), ixerisoside A 6'- O-acetate (3), ixerin N ( 4), ixerisoside A (5), ixerin M (6), tectroside (7), 8-epidesacylcynaropicrin glucoside (8), 8-epiisolipidiol (9), 11 βH-11,13-dihydrointegrifolin (10) 8 β-hydroxy-4 β,15-dihydrozaluzanin C (11), and integrifolin (12). Compounds 1-12 were evaluated for their inhibitory effect on the proliferation of the cultured human tumor cell lines MES-SA, MES-SA/DX5, HCT-15, and HCT15/CL02 in vitro.     

Cytotoxic sesquiterpene lactones fromSaussurea calcicola

Seven sesquiterpene lactones were isolated by the chromatographic separation of the MeOH extract of the aerial parts of Saussurea calcicola (Compositae). Their structures were determined spectroscopically to be cynaropicrin (1), arguerin B (2), cebellin F (3), 8alpha-hydroxy-11alpha, 13-dihydrozaluzanin C (4), desacylcynaropicrin (5), 3beta-hydroxy-8alpha-epoxymethylacriloiloxy-4(15),10(14),11(13)-trien-guaian-6,12-olide (6), and kandavanolide (7). Compounds 1 and 2 showed significant cytotoxicity against five cultured human tumor cell lines with ED50 values ranging from 0.23-1.72 microg/mL.     

Eremophilane sesquiterpene lactones from Ligularia virgaurea ssp. oligocephala

From an extract of the whole plant of Ligularia virgaurea ssp. oligocephala, three new eremophilane sesquiterpene lactones, 10alpha-hydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (1), 6alpha,10alpha-dihydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (2), 6beta,10beta-dihydroxyeremophila-7(11),8(9)-dien-12,8-olide (3), as well as four known sesquiterpene lactones with the same carbon skeleton, named toluccanolides A-C (4, 5, 7) and 6beta-hydroxy-8alpha-methoxyeremophila-1(10),7(11)-dien-12,8beta-olide (6) were isolated. Their structures were elucidated by spectroscopic methods including intensive 2D NMR techniques (gCOSY, gHMQC, gHMBC and 1H-1H NOESY for 2) and HR-ESI-MS.     

A New Sesquiterpene Lactone from Tsoongiodendron Odorum Chun

Abstract

A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5α, 6α, 7β, 10β-11α, 13-dihydro-4(15)-eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X-ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines.     

New sesquiterpene lactones from Laurus nobilis leaves as inhibitors of nitric oxide production

Two new metabolites 5alphaH,7alphaH-eudesman-4alpha,6alpha,11,12-tetraol (1) and 1beta,15-dihydroxy-5alphaH,7alphaH-eudesma-3,11(13)-dien-12,6alpha-olide ( 2) have been isolated from the methanolic extract of Laurus nobilis L. leaves. Their structures were determined through analysis of their one- and two-dimensional NMR spectral data ((1)H- and (13)C-NMR, DEPT, COSY, HMQC, HMBC and ROESY). The relative stereochemistry is proposed on the basis of combined J-based configuration analysis and ROESY data. In addition, three known sesquiterpene lactones santamarine (3), reynosin (4) and costunolide (5) along with blumenol C (6) were isolated and identified by spectral means. The isolated compounds 1 - 6 were found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophages. The most active compound 2 potently inhibited NO (2)(-) release with an IC (50) value of 0.8 microM.     

Stereoselective hydrogenation on the exocyclic and conjugated double bond of sesquiterpene lactones by Aspergillus versicolor D-1

Aspergillus versicolor D-1 was employed to convert dehydrocostuslactone (1) and 3-hydroxy-1(10),3,11(13)-guaiatriene-12,6-olide-2-one (5) stereoselectively. The reactions occurring were specific hydrogenation on the exocyclic α,β-double bond of sesquiterpene lactones with excellent conversion. Products were identified by the analysis of their spectra such as UV, IR, MS, ¹H, ¹³C NMR, and NOESY, and the structure of one new compound was elucidated. The characteristic of the stereoselective hydrogenation was also discussed and suggested.     

Two new cytotoxic ent-clerodane diterpenoids from Scutellaria barbata

Two new ent-clerodane diterpenoids have been isolated from Scutellaria barbata, and their structures were established by detailed spectroscopic analyses as (13R)-6α,7β-dihydroxy-8β,13-epoxy-11β-nicotinyloxy-ent-clerodan-3-en-15,16-olide (scutelinquanine D, 1) and (11E)-6α-acetoxy-7β,8β-dihydroxy-ent-clerodan-3,11,13-trien-15,16-olide (6-acetoxybarbatin C, 2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer cell lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC₅₀ values in the range of 2.5–6.6 μM.     

Sesquiterpene lactones with potent cytotoxic activities from Vernonia chinensis

Five new sesquiterpene lactones, namely vernchinilides A-E (1-5), along with five known compounds, 8 beta-(2-methylacryloyloxy)hirsutinolide 13-O-acetate (6), 8 alpha-(2-methylacryloyloxy)-1beta,4beta-epoxy-1alpha-methoxy-13-O-acetate-10 betaH-germacra-5 E,7(11)-dien-12,6-olide (7), 8 beta-(2-hydroxymethylacryloyloxy)hirsutinolide 13-O-acetate (8), 8 alpha-tigloyloxyhirsutinolide 13-O-acetate ( 9) and vernolide-B (10) were isolated from Vernonia chinensis. The structures of these new compounds were elucidated on the basis of spectral data, especially 2D-NMR techniques. Compounds 2, 5 and 6 exhibited potent cytotoxic activities against P-388 and A-549 tumor cell lines.     

赤芝子实体中三萜化学成分的研究

自赤芝[Ganoderma lucidum (Fr.)Karst]的二氯甲烷溶解部分分离得到一个新的三萜内酯化合物,命名为灵芝内酯(ganolactone)。根据光谱(UV,IR,¹HNMR,¹³CNMR,MS和2DNMR)解析,确定其结构为I式。同时还从赤芝子实体中分到三个已知化合物,即灵芝醇A(ganoderiolA,II),灵芝醇B(ganoderiolB,II)和灵芝三醇(ganodermatriolIV)。     

新疆雪莲化学成分的研究

从新疆雪莲的全草中分离得到一种新倍半萜内酯,根据红外光谱,核磁共振谱,质谱等证明了其结构式为1,并命名为雪莲内酯(Xuelianlactonc)。     

Two new cytotoxic ent-clerodane diterpenoids from Scutellaria barbata

Two new ent-clerodane diterpenoids have been isolated from Scutellaria barbata, and their structures were established by detailed spectroscopic analyses as (13R)-6α,7β-dihydroxy-8β,13-epoxy-11β-nicotinyloxy-ent-clerodan-3-en-15,16-olide (scutelinquanine D, 1) and (11E)-6α-acetoxy-7β,8β-dihydroxy-ent-clerodan-3,11,13-trien-15,16-olide (6-acetoxybarbatin C, 2). In vitro, the isolated two new compounds showed significant cytotoxic activities against three human cancer cell lines (HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells), and gave IC(50) values in the range of 2.5-6.6?μM.     

New guaiane, megastigmane and eudesmane-type sesquiterpenoids and anti-inflammatory constituents from Youngia japonica

Eleven sesquiterpenoids have been isolated from the whole plants of Youngia japonica (Asteraceae). Among these sesquiterpenoids, five were identified as new compounds on the basis of spectroscopic methods and chemical analysis. Their structures were 3-oxo-8alpha-(4-hydoxyphenyl)acetoxy-10(14),11(13)-guaiadien-12,6-olide ( 1), 3beta-[3-(4-hydroxyphenyl)acetyl-beta- D-glucopyranosyloxy]-8alpha-hydroxy-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 2), 3beta-[3-(4-hydroxyphenyl)acetyl-beta- D-glucopyranosyloxy]-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 3), 3alpha,5beta,6alpha-trihydroxy-4alpha-(beta- D-glucopyranosyloxy)-7-megastigmen-9-one ( 4), and 3alpha-(beta- D-glucopyranosyloxy)-4(15),11(13)-eudesmadien-12-oic acid ( 5). The three known components 3beta-(beta- D-glucopyranosyloxy)-8alpha-(4-hydroxyphenyl)acetoxy-4(15),10(14),11(13)-guaiatrien-12,6-olide ( 8), 3beta-(beta- D-glucopyranosyloxy)-4(15),10(14),11 (13)-guaiatrien-12,6-olide ( 9), and 3alpha-hydroxy-4alpha-(beta- D-glucopyranosyloxy)-5,7-megastigmadien-9-one ( 11) showed inhibitory activity against the proliferation of T and B lymphocytes of mice in vitro at concentrations of 1 x 10 ( - 7), 1 x 10 ( - 6), and/or 1 x 10 ( - 5) M without obvious cytotoxicity. Compound 9, the major component of the plant extract, exhibited weak anti-inflammatory activity at a dosage of 50 mg/kg ( p. o.) in in vivo anti-inflammatory experiments of mice.