Cytotoxic flavaglines and bisamides from Aglaia edulis

Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'-methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O-acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9), were isolated from the bark of Aglaia edulis, along with one known cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides, aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin, and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or twigs of this species. The structures of the new compounds (2-13) were elucidated by interpretation of their spectroscopic data. All isolates obtained in this study were evaluated for cytotoxicity against both several human cancer cell lines (Lu1, LNCaP, and MCF-7) and a nontumorigenic (HUVEC) cell line. Among these isolates, the cyclopenta[b]benzofurans (1-3) exhibited potent in vitro cytotoxic activity (ED50 range 0.001 to 0.8 microg/mL). Aglaroxin A 1-O-acetate (2) was further evaluated in the in vivo P388 lymphocytic leukemia model, by intraperitoneal injection, but found to be inactive in this model.     

Triterpenoids and steroids from the fruits of Melia toosendan and their cytotoxic effects on two human cancer cell lines

Ten new triterpenoids, named meliasenins I-R (1-10), one new steroid (11), and 11 related known compounds (12-22) were isolated from fruits of Melia toosendan. The structures of the new compounds were established on the basis of spectroscopic methods, including 2D NMR techniques and mass spectrometry. The relative configuration of 1, (20R*,23E)-25-hydroperoxyeupha-7,23-diene-3β,16β-diol (meliasenin I), was confirmed by single-crystal X-ray diffraction analysis. All isolated triterpenoids (1-10, 12-15) and two steroids (11, 20) were tested for their cytotoxicity against U20S human osteosarcoma and MCF-7 human breast cancer cells using the MTT assay, and some of them were significantly cytotoxic (IC(50) <10 μg/mL). The insecticidal properties of compounds 1-15 and 20 were also briefly evaluated.     

Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus activation

A new triterpene acid, lucidenic acid P (1a), and two new triterpene acid methyl esters, methyl lucidenates P (1b) and Q (2b), were isolated and characterized from the fruiting body of the fungus Ganoderma lucidum. Their structures were elucidated on the basis of spectroscopic methods. In addition, eight known triterpene acids, lucidenic acids A (3a), C (4a), D(2) (5a), E(2) (6a), and F (7a) and ganoderic acids E (9a), F (10a), and T-Q (11a), and six known triterpene acid methyl esters, methyl lucidenates A (3b), D(2) (5b), E(2) (6b), F (7b), and L (8b) and methyl ganoderate F (10b), were isolated and identified from the fungus. All of the triterpenoids, with the exception of 7a, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (96-100% inhibition at 1 x 10(3) mol ratio/TPA).     

Biologically active polyketide metabolites from an undetermined fungicolous hyphomycete resembling Cladosporium

Eight new polyketide-derived metabolites [cladoacetals A and B (1 and 2), 3-(2-formyl-3-hydroxyphenyl)propionic acid (3), 3-deoxyisoochracinic acid (4), isoochracinol (5), 7-hydroxy-3-(2,3-dihydroxybutyl)-1(3H)-isobenzofuranone (6), (+)-cyclosordariolone (10), and altersolanol J (11)] and six known metabolites [two isomeric 1-(1,3-dihydro-4-hydroxy-1-isobenzofuranyl)butan-2,3-diols (7a/b), 7-hydroxy-1(3H)-isobenzofuranone (8), isoochracinic acid (9), altersolanol A (12), and macrosporin (13)] have been isolated from solid-substrate fermentation cultures of an undetermined fungicolous isolate (NRRL 29097) that resembles Cladosporium sp. All structures were assigned primarily by analysis of 1D and/or 2D NMR data. Five of the compounds showed antibacterial activity.     

Antiplasmodial triterpenoids from Ekebergia capensis

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.     

Diterpenes, sesquiterpenes, and a C15-acetogenin from the marine red alga Laurencia mariannensis

In addition to 10 known compounds (7- 16), one new brominated diterpene, 10-hydroxykahukuene B (1), two new sesquiterpenes, 9-deoxyelatol (2) and isodactyloxene A (3), one new brominated C 15-acetogenin, laurenmariallene (4), and two new naturally occurring halogenated sesquiterpenes (5 and 6) that were previously obtained as intermediates in a biomimetic synthetic study of rhodolaureol and rhodolauradiol have been isolated and identified from the organic extract of the marine red alga Laurencia mariannensis. The structures of these compounds were established by spectroscopic methods. The antibacterial and antifungal activities of new compounds 1-4 were evaluated.     

Nematocidal thiocyanatins from a southern Australian marine sponge Oceanapia sp

Investigations of a southern Australian marine sponge, Oceanapia sp., have yielded two new beta methyl branched bisthiocyanates, thiocyanatins D1 (3a) and D(2) (3b), along with two new thiocarbamate thiocyanates, thiocyanatins E1 (4a) and E2 (4b). The new thiocyanatins belong to a rare class of bioactive marine metabolite previously only represented by thiocyanatins A-C (1, 2a/b). Structures were assigned on the basis of detailed spectroscopic analysis, with comparisons to the known bisthiocyanate thiocyanatin A (1) and synthetic model compounds (5-7). The thiocyanatins exhibit potent nematocidal activity, and preliminary structure-activity relationship investigations have confirmed key characteristics of the thiocyanatin pharmacophore.     

Steroidal triglycosides, kurilensosides A, B, and C, and other polar steroids from the Far Eastern starfish Hippasteria kurilensis

Three novel steroidal triglycosides, designated as kurilensosides A, B, and C (1- 3), were isolated along with a new steroidal diglycoside, kurilensoside D (4), and two new (6, 7) and one known (5) polyhydroxysteroid from the alcoholic extract of the Far Eastern starfish Hippasteria kurilensis. Compounds 1-3 are the first triglycosides containing two carbohydrate chains found from starfish. The structures of 1-7 were elucidated by spectroscopic methods (mainly 2D NMR) and chemical derivatization. Glycosides 1-4 and steroids 6 and 7 inhibited sea urchin egg fertilization by sperm preincubated with these compounds.     

毛酸浆的化学成分研究

对毛酸浆的干燥宿萼95%乙醇提取物的二氯甲烷部分进行化学成分的研究。利用正相硅胶柱色谱及反相制备高效液相色谱等方法分离纯化,得到10个化合物,通过质谱、一维及二维核磁共振波谱等手段对这些化合物的化学结构进行了鉴定,分别为5-O-(E-feruloyl)blumenol(1),异香草醛(2),反式对羟基肉桂酸乙酯(3),对羟基苯甲醛(4),对甲苯酚(5),反式肉桂酸甲酯(6),7,3',4'-三甲氧基槲皮素(7),5,3', 5'-三羟基-3,7,4'-三甲氧基黄酮(8),danielone(9),5,5'-二异丁氧基-2,2'-联呋喃(10),其中化合物1为新化合物,化合物7~10为首次从该属植物中分离得到。     

Chromophenazines from the terrestrial Streptomyces sp. Ank 315

The new chromophenazines A-F [9-methyl-5-(3'-methylbut-2'-enyl)-5H-benzo[a]phenazin-7-one (1a), 9-methyl-5-(3'-methylbut-2'-enyl)-7-oxo-5,7-dihydrobenzo[a]phenazine-1-carboxylic acid (1b), 5-(3'-methylbut-2'-enyl)-7-oxo-5,7-dihydrophenazine-1-carboxamide (2), 3-benzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxylic acid (5a), 3,7-dibenzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxylic acid (5b), and 3,7-dibenzoyl-5-(3'-methylbut-2'-enyl)-5,10-dihydrophenazine-1-carboxamide (5c)], together with phenazine-1-carboxylic acid, 1-phenazinecarboxamide, 1-phenazinol, tryptophol, and anthranilic acid, were isolated from Streptomyces sp. Ank 315. The structures of the new compounds were established on the basis of spectroscopic data, 1D NOE, 2D NMR, and ESIMS measurements and comparison with literature values.     

New antioxidant hydroquinone derivatives from the algicolous marine fungus Acremonium sp

A marine fungal isolate, identified as Acremonium sp., was mass cultivated and found to produce two novel hydroquinone derivatives, 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol (1) and 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol-5-beta-D-glucopyranoside (2). Compound 1 and its glucoside 2 possess a most unusual ring system. The new natural products (3R,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)naphthalenone (3) and (3S,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)-naphthalenone (4) were obtained as a 1:0.8 mixture. 2-(1-Methylethylidene)pentanedioic acid (5) was isolated for the first time as a natural product and its structure proven by X-ray analysis. In addition to these compounds an inseparable mixture of three new isomeric compounds, pentanedioic acid 2-(1-methylethylidene)-5-methyl ester (6), pentanedioic acid 2-(1-methylethylidene)-1-methyl ester (7), and pentanedioic acid 2-(1-methylethenyl)-5-methyl ester (8), was also obtained. Isolated together with the new compounds were three known hydroquinone derivatives, 9, 10, and 11. The structures of all compounds were determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, and IR). Each isolate was tested for its antioxidant properties, and compounds 1 and 9-11 were found to have significant activity.     

Cytotoxic germacranolides and acyclic diterpenoides from the seeds of Carpesium triste

Four new highly oxygenated germacranolides (1, 4, 6, and 7) and four new acyclic diterpenes (8-11), along with three known germacranolides (2, 3, and 5), were isolated from the seeds of Carpesium triste. The structures of the new compounds were elucidated by spectroscopic methods including IR, HRESIMS, and 1D and 2D NMR experiments, and the absolute configurations of compounds 1 and 8-10 were established by CD and Mosher's methods, respectively. Compounds 1, 2, and 4-10 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), HL-60 (human promyelocytic leukemia), and L02 (human hepatocyte) cell lines. Compounds 1, 2, and 4-7 exhibited significant cytotoxicity against HL-60 cells, and compound 10 exhibited cytotoxicity against SMMC-7721 cells.     

Kopetdaghins A-E, sesquiterpene derivatives from the aerial parts and the roots of Dorema kopetdaghense

Three new sesquiterpene derivatives, kopetdaghins A-C (1-3), one known prenylated coumarin (7), and two known steroid glucosides, sitosterol 3-O-glucoside and stigmasterol 3-O-glucoside, were isolated from the aerial parts of Dorema kopetdaghense. In addition, two new sesquiterpene derivatives, kopetdaghin D (4) and kopetdaghin E (5), together with kopetdaghins A-C and one known sesquiterpene coumarin (6), were isolated from the roots of the plant. The structures of these compounds were elucidated by various 1D and 2D NMR techniques as well as high-resolution positive-ion ESIMS.     

Synthesis of A-seco derivatives of betulinic acid with cytotoxic activity

In this study, the relationships between the chemical structure and cytotoxic activity of betulinic acid (1) derivatives were investigated. Eight lupane derivatives (1-8), one of them new (6), five diosphenols (9-13), four of them new (10-13), two new norderivatives (14 and 15), five seco derivatives (16-20), four of them new (16, 17, 19, and 20), and three new seco-anhydrides (21-23) were synthesized from 1, and their activities were compared with the activities of known compounds. The effects of substitution on the A-ring and esterification of the carboxyl group in position 28 on cytotoxicity were of special interest. Significant cytotoxic activity against the T-lymphoblastic leukemia cell line CEM was found in diosphenols 9 and 13 (TCS(50) 4 and 5 micromol/L) and seco-anhydrides 22 and 23 (TCS(50) 7 and 6 micromol/L). All compounds were also tested on cancer cell lines HT 29, K562, K562 Tax, and PC-3, and these confirmed activity of diosphenols 9, 10, and 11 and anhydride 22. Diosphenols, as the most promising group of derivatives, were further tested on four more lines (A 549, DU 145, MCF 7, SK-Mel2).     

土茯苓内生芒果球座菌的次级代谢产物及其抗肿瘤活性研究

目的研究土茯苓内生芒果球座菌Guignardia mangiferae的次级代谢产物及其抗肿瘤活性。方法采用硅胶柱、反相硅胶柱、凝胶柱和制备薄层色谱等色谱技术进行分离纯化,通过现代波谱技术进行结构鉴定;以神经胶质瘤细胞SF-268、乳腺癌细胞MCF-7、大细胞肺癌细胞NCI-H460为供试细胞株,采用SRB法对化合物进行体外抗肿瘤活性研究。结果从土茯苓内生芒果球座菌的100 L液体发酵提取物中分离得到12个化合物,经波谱数据分析鉴定其中10个化合物,分别为15-hydroxyl tricycloalternarene 5b(1)、guignardiaene D(2)、guignardiaene C(3)、guignardone A(4)、guignardone B(5)、3-(4-甲苯氧基)-丙酸(6)、2,4-壬二醇(7)、麦角甾酮(8)、酪醇(9)、对羟基苯甲醛(10)。杂合萜类化合物1～5对SF-268细胞具有选择性的抑制作用,化合物6、7对MCF-7细胞具有选择性的抑制作用。结论化合物6～10均为首次从该属真菌中得到,其中化合物6、7为新的天然产物。     

Daphnane- and tigliane-type diterpenoid esters and orthoesters from Pimelea elongata

Investigation of Pimelea elongata ("Lakebed Pimelea") afforded 18 tigliane- and daphnane-type diterpenes (1-18). Eight of these were new compounds: four (1-3, 5) tigliane esters and four (7, 8, 10, 11) daphnane orthoesters. The 10 known compounds were 12-O-decanoylphorbol-13-acetate (4), P. simplex subtoxin B (6), wikstroelide E (9), pimelotides A and B (12, 13), gnidiglaucin (14), simplexin (15), huratoxin (16), kirkinine D (17), and 12-β-acetoxyhuratoxin (18). The structures and relative configurations of the new compounds were determined by 1D and 2D NMR spectroscopic studies in combination with MS analyses.     

Three new sesquiterpenes from Croton arboreous

Three new sesquiterpenes, 5alpha,7alpha,10betaH-3-patchoulen-2-one (1), 5alpha,7alpha10betaH-4(14)-patchoulen-2alpha-ol (2), and 9alpha,10beta-dihydroxy-2beta,4beta-peroxy-1alpha,5beta,7alphaH-guaiane (3), were isolated from the aerial parts of Croton arboreous along with 14 known compounds. The structures of these compounds were determined on the bases of their spectroscopic data (IR, UV, OR, 1D and 2D NMR, and MS). The anti-inflammatory activity against ear edema in mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated for all the pure compounds and showed that compounds 4-7 are active.     

New phenylpropenoids, bis(1-phenylethyl)phenols, bisquinolinone alkaloid, and anti-inflammatory constituents from Zanthoxylum integrifoliolum

Five new compounds, including two new phenylpropenoids, (R,E)-1-[4-(3-hydroxyprop-1-enyl)phenoxy]-3-methylbutane-2,3-diol (1) and 4-hydroxy-3-(3-methyl-2-butenyl)cinnamyl alcohol (2), two new bis(1-phenylethyl)phenols, 2,6-bis(1-phenylethyl)phenol (3) and 2,4-bis(1-phenylethyl)phenol (4), and a new bisquinolinone alkaloid, 18-demethylparaensidimerin C (5), together with 17 known compounds have been isolated from the stem wood of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses including extensive 2D nuclear magnetic resonance data. Among the isolates, N-methylflindersine (7), (-)-simulanol (10), and evofolin-C (16) exhibited potent inhibition against N-formylmethionylleucylphenylalanine-induced superoxide production with IC(50) values less than 12 microM.     

Bioactive bibenzyl derivatives and fluorenones from Dendrobium nobile

Bioassay-guided fractionation of the 60% ethanol extract of the stems of Dendrobium nobile using the DPPH assay led to the isolation of two new bibenzyl derivatives, nobilin D (1) and nobilin E (2), and a new fluorenone, nobilone (3), together with seven known compounds (4-10). Their structures were determined on the basis of spectroscopic analyses. Compounds 1, 2, 4, 7, 8, and 10 exhibited significant antioxidant activity higher than or equivalent to vitamin C in the DPPH assay, and compounds 1, 3, 4, and 7-10 displayed higher antioxidant activity than vitamin C in the ORAC assay. Compounds 1, 2, and 10 also exhibited stronger inhibitory effects on NO production than resveratrol.