A cytotoxic butenolide,two new dolabellane diterpenoids,a chroman and a benzoquinol derivative formosan Casearia membranacea

Investigation of a cytotoxic chloroform-soluble fraction of the stem of Casearia membranacea (Flacourtiaceae) led to the isolation of five new compounds, including one butenolide, casealactone (1), one chroman, caseamemin (2), two dolabellane diterpenoids, casearimene A (3) and casearimene B (4), one benzoquinol ether, casearinone (5), together with fifteen known compounds, including two amides, N- trans-feruloyltyramine (6) and N- cis-feruloyltyramine (7), six steroids, beta-sitosterol (8), stigmast-5-ene-3beta,7alpha-diol (9), stigmast-5-ene-3beta,7beta-diol (10), stigmastane-3beta,5alpha,6beta-triol (11), beta-sitostenone (12), beta-sitosterol 3- O-beta-glucoside (13), two triterpenoids, squalene (14) and friedelin (15), one lignan, (+/-)-syringaresinol (16), two benzenoids, syringaldehyde (17) and vanillic acid (18), one ester, methyl hexadecanoate (19), and anthraquinone (20), respectively. Among these isolates, 1 showed cytotoxicity against P-388 and HT-29 cancer cell lines in vitro, and 6 and 7 showed cytotoxicity against the P-388 cancer cell line. The structures of these compounds were determined by means of spectroscopic techniques, and the structure of 3 was confirmed by X-ray crystallographic analysis.     

Neoclerodane diterpenoids from Scutellaria barbata

Eight new neoclerodane diterpenoids (1- 8), scutebatas H-O, together with eight known compounds, have been isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated on the basis of spectroscopic studies. In vitro cytotoxicity of selected compounds against cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480 was evaluated. Compounds 5, 6, 7 showed moderate cytotoxicities against several human cancer cell lines, with IC50 values ranging from 12.6-31.4?μM. In addition, compound 1 showed selective cytotoxicity against MCF-7.     

19-oxygenated ent-kaurane diterpenoids from Isodon pharicus

Eight new 19-oxygenated ENT-kaurane diterpenoids were isolated from the aerial parts of Isodon pharicus. Their structures were determined by means of extensive spectroscopic techniques including interpretation of 1D and 2D?NMR spectra. Selected compounds were evaluated for their cytotoxicity against NB4, A549, PC-3, MCF-7, and SH-SY5Y cell lines.     

Two novel ent-kauranoid diterpenoids from Isodon japonica leaves

Two novel ent-kaurane diterpenoids, taihangjaponicain A (1), and taihangjaponicain B ( 2), and nine known diterpenoids, epinodosin (3), oridonin (4), epinodosinol (5), lasiokaurin ( 6), 1alpha- O-beta- D-glucopyranosylenmenol (7), lasiodonin (8), rabdosichuanin D ( 9), shikokianin (10) and rabdoternin A (11) were isolated from I. japonica leaves. The structures of the two new compounds were elucidated using 1-D and 2-D NMR spectroscopy. Compounds 1 and 3 - 11 were tested against HL-60, HO-8910 and A-549 human tumor cells. Compounds 4, 6 and 10 showed significant cytotoxicity against HL-60 cells with IC (50) values of 4.6, 2.0 and 3.4 microM, respectively, and against A-549 cells with IC (50) values of 17.5, 11.4 and 18.8 microM, respectively. Compound 6 exhibited moderate cytotoxicity against HO-8910 cells with an IC (50) value of 17.9 microM.     

A new phenolic compound with anticancer activity from the wood of Millettia leucantha

A new phenolic compound, 1-(3-hydroxy-4-methoxyphenyl)-3-(2,4-dihydroxy-5-methoxyphenyl) propan-1-ol, named as millettinol (1), along with six known compounds, medicarpin (2), 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (3), 5,4'-dihydroxy-7,8-dimethoxyisoflavone (4), physcion (5), (R)-(-)-mellein (6) and isoliquiritigenin (7), were isolated from the wood of Millettia leucantha. The structures of the compounds were determined by an analysis of their spectroscopic data. Some of the isolates were tested for anticancer activity. Compound 1 exhibited strong cytotoxicity against the BCA-1 tumor cell lines with an IC(50) = 3.44 μg/mL.     

Diterpenoids from the roots of Euphorbia fischeriana

Six tigliane-type diterpenoids (1-6) were isolated from the roots of Euphorbia fischeriana. Their structures were elucidated by various spectral analyses. Among them, compounds 1 and 3 were new, and compounds 2, 4, and 5 were naturally obtained for the first time. All compounds were tested against two human cancer cell lines, MDA-MB-231 and HepG2, and one human immortalized cell line, and only compound 6 showed cytotoxicity for MDA-MB-231 cells with an IC(50) value of 6.694 μM.     

Diterpenoids including a novel dimeric conjugate from Salvia leriaefolia

Salvialeriafone (1), a novel diterpene-norditerpene conjugate, was isolated from Salvia leriaefolia. Additionally, two new abietane-type diterpenoids, salvialerial (2) and salvialerione (3), as well as four known compounds, sugiol (4), salvicanaric acid (5), dehydroroyleanone (6), and cariocal (7), were isolated and identified. Their structures were determined by spectroscopic data analyses. Known compounds were isolated from this plant for the first time. Compounds 1, 5, 6, and 7 exhibited IN VITRO antiproliferative activity against the human cervical cancer cell line (Hela), while 6 showed cytotoxicity against the human prostate cancer cell line (PC3).     

Cytotoxic terpene hydroperoxides from the aerial parts ofAster spathulifolius

Three new sesquiterpene hydroperoxides, 1-[3-(2-hydroperoxy-3-methylbut-3-en)-4-hydroxyphenyl]ethanone (2), 7beta-hydroperoxy-eudesma-11-en-4-ol (3), and 7alpha-hydroperoxymanool (4), together with three known compounds, germacrone (1), ent-germacra-4(15),5,10(14)-trien-1alpha-ol (5) and teucdiol A (6) were isolated from the aerial parts of Aster spathulifolius (Compositae). Their structures were characterized using chemical and spectroscopic methods. The isolated compounds were tested for their cytotoxicity against five human tumor cell lines in vitro using a SRB method. The two new compounds, 3 and 4, showed moderate cytotoxicity against human cancer cells with ED50 values ranging from 0.24 to 13.27 microg/mL.     

A new rearranged abietane diterpenoid from Clerodendrum kaichianum Hsu

A new abietane diterpenoid, (3S,16R)-12,16-epoxy-3,6,11,14,17-pentahydroxy-17(15?→?16)-abeo-5,8,11,13-abietatetraen-7-one (1), was isolated from the stems of Clerodendrum kaichianum Hsu, together with four known diterpenoids. The structures of the isolated compounds were assigned on the basis of their NMR spectra including 2D NMR techniques such as COSY, HMQC, and HMBC experiments, and were compared with those of the literature data. This new compound showed significant cytotoxicity against the HL-60 and A-549 tumor cell lines.     

Isolation of limonoids and alkaloids from<Emphasis Type="Italic">Phellodendron amurense</Emphasis> and their multidrug resistance (MDR) reversal activity

Three limonoids and five alkaloids were isolated from the chloroform layer of the MeOH extract of the bark of Phellodendron amurense (Rutaceae). The structures of the compounds isolated were determined to be obacunone (1), limonin (2), 12alpha-hydroxylimonin (3), gamma-fagarine (4), oxyberberine (5), canthin-6-one (6), 4-methoxy-N-methyl-2-quinolone (7) and oxypalmatine (8) based on the physicochemical and spectroscopic data. Compounds 3, 5, 7, and 8 were first isolated from the Phellodendron amurense. The isolated compounds were then tested for their cytotoxicity against five human tumor cell lines in vitro using the SRB method. Compound 5 showed significant cytotoxicity against the five tumor cell lines with ED50 values ranging from 0.30 to 3.0 microg/mL. The marginal or noncytotoxic compounds (1, 2, 3, 4, and 7) were examined for their P-gp related MDR reversal activities. Compound 1 showed significant P-gp MDR inhibition activity in MES-SA/DX5 and HCT15 cells with an ED50 value of 0.028 microg/mL and 0.0011 microg/mL, respectively.     

Anti-inflammatory and cytotoxic diterpenes from formosan Polyalthia longifolia var. pendula

A new clerodane diterpenoid 16-hydroxycleroda-13-ene-15,16-olide-3-one (1) was isolated from the bark of Polyalthia longifolia var. pendula, along with 23 known compounds and phytosteroids. Among these compounds, 5 - 7, 10, and 24 were obtained for the first time from the family Annonaceae . The structures of the isolated compounds were determined by mass and spectroscopic analysis. The clerodane diterpenoids, 2 - 4, showed significant cytotoxicity towards Hep G2 and Hep 3B hepatoma cell lines. Furthermore, compound 5 exhibited potent anti-inflammatory activity towards formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide generation by neutrophils with IC50 = 0.60 +/- 0.09 microg/mL.     

New halimane diterpenoids from Croton oblongifolius

Three new halimane-type diterpenoids, crotohalimaneic acid ( 1), crotohalimoneic acid ( 2) and 12-benzoyloxycrotohalimaneic acid ( 3), were isolated from the stem bark of Croton oblongifolius Roxb. Their structures were established on the basis of spectroscopic and X-ray analysis. Compounds 1 and 2 showed non-specific strong cytotoxicity against a panel of human tumor cell lines; whereas 3 was inactive.     

Two new casbane diterpenoids from the roots of Euphorbia pekinensis

From the roots of Euphorbia pekinensis, two new casbane diterpenoids, named pekinenins A (1) and B (2), were isolated. Their structures were elucidated as 18-hydroxy-1βH,2αH-casba-3E,7E,11E-trien-5-one (1), 5α-methoxy-1βH,2αH-casba-3Z,7E,11E-trien-18-oic acid (2) by a combination of 1D and 2D NMR spectroscopy and mass spectrometry. In the cytotoxicity assay of the two new compounds against Hela, MCF-7, and C6 human cancer cell lines, compound 1 showed moderate cytotoxic activity against two human cancer cell lines, Hela and C6, with IC(50) values of 42.97 and 50.00?μM, respectively.     

Guanacastane-type diterpenoids from the insect-associated fungus Verticillium dahliae

Four new guanacastane-type diterpenoids, namely dahlianes A (1), B (2), C (3), and D (4), were isolated from cultures of Verticillium dahliae. Their structures were elucidated on the basis of extensive spectroscopic data analysis. Their absolute configurations were determined by a combination of Mo₂(OAc)₄-induced electronic circular dichroism experiment and Mosher ester method. In cytotoxicity evaluation against human tumor cell lines, compounds 2 and 3 exhibited significant cytotoxicities against MCF-7 cell lines with IC₅₀ values of 3.35 and 4.72 μM, respectively.     

Cytotoxic and COX-2 inhibitory constituents from the aerial parts ofAralia cordata

Three diterpenes (1, 8, and 9), three triterpenes (3, 4, and 7), one saponin (11), four sterols (2, 5, 6, and 12), and one cerebroside (10) were isolated from the EtOH extract of the aerial parts of Aralia cordata by repeated silica gel column chromatography. Their chemical structures were identified by comparing their physicochemical and spectral data with those published in literatures. All isolated compounds were evaluated for their cytotoxicity against L1210, K562, and LLC tumor cell lines using MTT assay. Of which, 3beta,5alpha-dihydroxy-6beta-methoxyergosta-7,22-diene (6) showed a potent cytotoxicity against all cell lines with IC50 values of 11.7, 11.9, and 15.1 microM, respectively, while compounds 1, 5, and 11 showed a moderate or weak cytotoxicity. These isolates were also examined for their inhibitory activity against COX-1 and COX-2. Although most compounds, except for 2, 10, and 12, showed a strong inhibitory activity against COX-1, they exhibited a moderate or weak inhibitory activity against COX-2.     

海南海桑内生真菌Bionectria ochroleuca HHS111023次生代谢产物的研究

目的 研究中国特有红树植物海南海桑内生真菌Bionectria ochroleuca HHS111023的次生代谢产物及其生物活性。方法 利用多种柱色谱技术对次生代谢产物进行分离纯化;通过核磁与质谱数据分析结合理化常数及文献比对,鉴定化合物的结构;分别采用纸片琼脂扩散法和MTT法对化合物的抗菌活性和细胞毒活性进行测试。结果 从海南海桑内生真菌Bionectria ochroleuca HHS111023的次生代谢产物中分离鉴定了7个化合物：Lasiodiplodin (1)、(R)-de-O-methyllasiodiplodin (2)、(5S)-5-hydroxylasiodiplodin (3)、 (5R)-5-hydroxylasiodiplodin (4)、methyl (E)-11,12,15-trihydroxyoctadec-13-enoate (5)、对羟基苯乙醇 (6)、对羟基苯乙酸甲酯 (7)。化合物1和2分别对白色念珠菌和青枯雷尔氏菌具有抗菌活性,且分别对SGC-7901和K-562具有体外细胞毒活性。结论 化合物1 ~ 4为首次从淡色生赤壳菌Bionectria ochroleuca次生代谢产物中分离得到,化合物5为首次分离自微生物次生代谢产物;海南海桑内生真菌Bionectria ochroleuca HHS111023能产生具有抗菌和细胞毒活性的化合物。     

Three new diterpenoids from the leaves of Thuja orientalis

Three new diterpenoids, 18-formyloxy-8 β-hydroxysandaracopimar-15-ene (1), 15(R)-N-butoxypinusolidic acid (2), and 15,16-dihydro-15,16-dimethoxylambertianic acid (3), along with twelve known compounds (4-15) were isolated from MeOH extracts of leaves of Thuja orientalis L. The structures of the three new compounds were elucidated on the basis of spectroscopic analyses, including extensive 2D-NMR data. The absolute stereochemistry of compound 2 was clarified by a CD spectroscopic study. The isolated compounds were evaluated for cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines in vitro using the sulforhodamin B (SRB) bioassay.     

Terpene and phenolic constituents of <Emphasis Type="Italic">Lactuca indica</Emphasis> L.

We isolated seven terpenes and five phenolic constituents from the aerial parts of Lactuca indica L. using column chromatographic separation of its MeOH extract. Their structures were determined by spectroscopic methods to be trans-phytol (1), 3beta-hydroxyglutin-5-ene (2), 5,6-epoxy-3-hydroxy-7-megastigmen-9-one (3), 11beta-13-dihydrolactucin (4), 2-phenylethyl beta-D-glucopyranoside (5), cichorioside B (6), 1-hydroxylinaloyl-6-O-beta-D-glucopyranoside (7), (6S,9S)-roseoside (8), benzyl-beta-D-glucopyranoside (9), 2-(3'-O-beta-D-glucopyranosyl-4'-hydroxyphenyl)-ethanol (10), 3-(beta-D-glucopyranosyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-dihydrobenzofuran (11), and (+)-taraxafolin-B (12). Compounds 1-3, 5, and 7-12 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay.     

Antiproliferative hopane and oleanane glycosides from the roots of Glinus lotoides

Three new hopane saponins, lotoidosides A - C (1 - 3), and four new oleanane saponins, lotoidosides D - G (4 - 7), were isolated from the roots of Glinus lotoides L. (Molluginaceae). Their structures were determined by extensive 1D- and 2D-NMR spectroscopy and ESI-MS analysis. The antiproliferative activity of compounds 1 - 7 was evaluated using three continuous murine and human culture cell lines J774.A1, HEK-293, WEHI-164. Compounds 1 and 3 - 7 showed significant cytotoxicity against the three cancer cell lines with IC50 values ranging from 0.018 to 0.62 microM, while compound 2 exerted a weak activity only against the cell line HEK-293.     

Oleanane-type triterpene saponins and cassaine-type diterpenoids from Erythrophleum fordii

Phytochemical investigation of the EtOH extract of the leaves of Erythrophleum fordii led to the isolation of two oleanane-type triterpene saponins (1-2) and five cassaine-type diterpenoids (4-8) along with one known methyl 3 β-hydroxy-erythrosuamate (3). Their structures were established by extensive NMR, as well as ESI-MS analyses and acid hydrolysis. Biological evaluation of compounds 3- 8 against five human cancer cell lines revealed that compounds 5-7 exhibited potent cytotoxic activity with IC?? values ranging from 1.51 to 8.68 μM.