Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2

As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.     

鞭打绣球中的一个新单萜苷

从鞭打绣球(Hemiphragma heterophyllum Wall.)全草中分离到1个新单萜苷和7个已知化合物.通过波谱数据分析,新单萜苷的结构鉴定为(4S)-α-萜烯醇-8-O-β-D-比喃木糖-(1→6)-β-D-比喃葡萄糖苷,已知化合物分别鉴定为globularin(2)、(2S 3S,4R,9E)-1,3,4-trihydroxy-2-[(2'R)-hydroxy-tetracosanoylamino]-9-octadecene(3)、β-香树素(4)、齐墩果酸(5)、肉桂酸(6)、β-谷甾醇(7)和胡萝卜甙(8).除化合物2外,其余化合物均为首次从鞭打绣球中分离得到.     

云南金钱槭茎化学成分

对云南金钱槭枝条部分的化学成分进行了研究,从其乙醇提取物中共分离鉴定了16个化合物,通过波谱学方法鉴定为:erythro-4,7,9-三羟基-3,3'-二甲氧基-8-O-4'-新木脂素-9'-O-β-D-吡喃葡萄糖苷(1),Hyugano-side IIIa(2),Hyuganoside IIIb(3),erythro-Buddlenol B(4),erythro-7',8'-Didehydrobuddlenol B(5),(±)-丁香脂素(6),臭矢菜素A(7),柑橘苷A(8),(4R)-p-薄荷-1-烯-7,8-二醇7-O-β-D-吡喃葡萄糖苷(9),2-甲氧基-3-(3-吲哚基)丙酸(10),肌苷(11),Tachioside(12),Isotachioside(13),3-O-(β-D-吡喃葡萄糖基)-1-(3,5-二甲氧基-4-羟基苯基)-1-丙酮(14),反式异松柏苷(15),4-[(E)-3-乙氧基-1-丙烯基]-2-甲氧基苯酚(16)。其中化合物5为新的倍半木脂素,其余化合物均首次从该属植物中分离得到。     

Arthrinins A-D: novel diterpenoids and further constituents from the sponge derived fungus Arthrinium sp

Bioassay-guided fractionation of a methanolic extract of the fungus Arthrinium sp., isolated from the Mediterranean sponge Geodia cydonium, afforded 10 natural products including five new diterpenoids, arthrinins A-D (1-4) and myrocin D (5). In addition, five known compounds were obtained, which included myrocin A (6), norlichexanthone (7), anomalin A (8), decarboxycitrinone (9) and 2,5-dimethyl-7-hydroxychromone (10). The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR and HR-MS analyzes. The absolute configuration of arthrinins A-D (1-4) was established by the convenient Mosher method performed in NMR tubes and by interpretation of the ROESY spectra. Antiproliferative activity of the isolated compounds was assessed in vitro against four different tumor cell lines, including mouse lymphoma (L5178Y), human chronic myelogenous leukemia (K562), human ovarian cancer (A2780) and cisplatin-resistant ovarian cancer cells (A2780CisR), using the MTT assay. Norlichexanthone (7) and anomalin A (8) exhibited the strongest activities with IC?? values ranging from 0.40 to 74.0 μM depending on the cell line investigated. This was paralleled by the inhibitory activity of both compounds against 16 cancer related protein kinases including aurora-B, PIM1, and VEGF-R2. In vitro IC?? values of 7 and 8 against these three protein kinases ranged from 0.3 to 11.7 μM. Further investigation of the potential antitumoral activity of compounds 5-8 was performed in an in vitro angiogenesis assay against human umbilical vascular endothelial cells (HUVEC) sprouting induced by vascular endothelial growth factor A (VEGF-A). Anomalin A (8), myrocin D (5) and myrocin A (6) inhibited VEGF-A dependent endothelial cell sprouting with IC?? values of 1.8, 2.6 and 3.7 μM, respectively, whereas norlichexanthone (7) was inactive.     

Terpenoid and phenolic metabolites from the fungus xylaria sp. associated with termite nests

Three new sesquiterpene acids, xylaric acids A-C (1-3, resp.), and a new tetralone (=3,4-dihydronaphthalen-1(2H)-one) derivative, 4, along with nine known compounds, xylaric acid D (5), hydroheptelidic acid (6), gliocladic acid (7), chlorine heptelidic acid (8), trichoderonic acid A (9), 16-(α-D-mannopyranosyloxy)isopimar-7-en-19-oic acid (10), 16-(α-D-glucopyranosyloxy)isopimar-7-en-19-oic acid (11), 5-carboxymellein (12), and naphthalen-1,8-diol 1-O-α-D-glucopyranoside (13) have been isolated from the solid culture of the ascomycete fungus Xylaria sp. associated with termite nest. The structures of these compounds were elucidated primarily by NMR experiments. The absolute configurations of compounds 1-3 and 5-9 were determined by combination of X-ray data and CD spectral analysis. The absolute configuration of 4 was assigned by Snatzke's method. Compounds 8 and 11 showed slight cytotoxicities against two cell lines A549 and SGC7901.     

Synthesis of 3-alkyl(aryl)-4-alkylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones and 3-alkyl-4-alkylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones as antitumor agents

A series of 3-alkyl-4-phenylethylidenamino- (8) and 3-alkyl-4-(3-phenylallylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (9) was synthesized from the reaction of the corresponding 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1), with phenylacetaldehyde and cinnamaldehyde. 3-Alkyl-4-(2-phenylethylamino)- (10) and 3-alkyl-4-(3-phenylpropylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (11) were obtained from the selective reduction of compounds (8) and (9) with NaBH₄. The in vitro antitumor activity of the novel compounds was screened and the highest inhibition of tree tumor cell lines was observed for the compounds containing phenylethylenamino and phenylethylamino groups at position 4 of 1,2,4-triazol ring.     

A new antifungal briarane diterpenoid from the gorgonian Junceella juncea Pallas

A new 8-hydroxy briarane diterpenoid (compound 1) with antifungal activity was isolated along with known compounds (2-5) from the gorgonian coral Junceellajuncea. On the basis of spectroscopic data (1D and 2D NMR, MS), the structure of the compound 1 was established as (1S,2S,8S,9S,10S,11R,12R,14S,17R)-11,20-epoxy-14-(3-methylbutanoyl)-2,9,12-triacetoxy-8-hydroxybriar-5(16)-en-18,7-olide. Compound 1 exhibited significant activity against fungi (Aspergillus niger, Candida albicans and Penicillium notatum) but the other compounds (2-5) did not exhibit the activity against fungi.     

Synthesis, and structural and biological studies of efrapeptin C analogues

A series of analogues of efrapeptin C (1), with variations in the central tripeptide epitope (positions 6-8), were prepared by a combination of solid- and solution-phase peptide syntheses. The conformations of the modified compounds 2-6 were investigated by circular-dichroism (CD) spectroscopy to differentiate between 3(10)- and alpha-helical secondary structures. The inhibitory activities of the new compounds towards F(1)-ATPase from E. coli were determined. The modified congeners 3-5 were less active by one order of magnitude compared to 1 (K(i) 10 microM), and 6 was completely inactive. Our experiments demonstrate that the flexible, central tripeptide epitope, comprising positions 6-8 in 1, is crucial for molecular recognition, even slight sequence modifications being hardly tolerated.     

Chemistry of New Zealand Apiaceae: a rare phenylpropanoid and three new germacrane derivatives from Anisotome lyallii

A phytochemical investigation of the New Zealand endemic Apiaceae species Anisotome lyallii Hook.f. yielded (+)-alpha-angeloyloxylatifolone (1), 6-O-angeloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (2), 6-O-tigloyl-8-O-tigloyl-6beta,8alpha,11-trihydroxygermacra-1(10)E,4E-diene (3) and 6-O-tigloyl-8-O-tigloyl-1alpha,6beta,8alpha,11-tetrahydroxygermacra-4E,10-(14)diene (4). The structures were elucidated by HR mass spectrometry and 1D- and 2D-NMR spectroscopy. A chemosystematic survey for compounds 1-3 in other New Zealand Apiaceae by HPLC-MS revealed that 1-3 were confined to A. haastii Cockayne & Laing and A. lyallii, and that some minor compounds in other species of Anisotome were isomers of 2 and 3.     

Antibacterial and cytotoxic activity of prenylated bicyclic acylphloroglucinol derivatives from Hypericum amblycalyx

Two new bicyclic acylphloroglucinol derivatives, hypercalyxone A (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 1) and B (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 2), have been isolated from the petroleum ether extract of the aerial parts of Hypericum amblycalyx, together with two further compounds (1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 3 and 1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 4), which have been described only as semi-synthetic products. In addition, the known triterpene lup-20(29)-en-3-one was obtained. Structure elucidation was based on 1D and 2D NMR studies, as well as on data derived from mass spectrometry. The four acylphloroglucinol derivatives were evaluated for their cytotoxic and antibacterial activity. All compounds showed moderate cytotoxic activity against KB and Jurkat T cancer cells. Especially compounds 3 and 4 exhibited a strong antibacterial activity against different Gram-positive strains.     

The chemical constituents of the fungus Stereum sp

Four new compounds, including a sesquiterpene and three aromatic compounds, and a known compound were isolated from a culture broth of the fungus Stereum sp. The novel sesquiterpene was determined to be stereumone A ((+)-2,3,4a,5,6,7,8a,9-octahydro-5-hydroxy-6,6,9-trimethyl-4,8a-epoxynaphtho[2,3-b]furan-8(8H)-one; 1), and the three new aromatic compounds were elucidated as 3,5-dihydroxy-4-(3-methylbut-2-enyl)benzene-1,2-dicarbaldehyde (2), 5,7-dihydroxy-6-(3-methylbut-2-enyl)isobenzofuran-1(3H)-one (3), butyl 2,4-dihydroxy-6-methylbenzoate (4), together with the known compound methyl 2,4-dihydroxy-6-methylbenzoate (5). The structures were established by spectroscopic methods including 2D-NMR techniques. Compounds 2 and 4 showed evident nematicidal activity against nematode Panagrellus redivivus.     

Three types of sesquiterpenes from rhizomes of Atractylodes lancea

Eight sesquiterpenes, including four guaiane-types containing an interesting epoxy unit (1-4), a rare tricyclic carbon skeleton-type (5) and three eudesmane-types (6-8), along with five known compounds, were isolated from rhizomes of Atractylodes lancea. The structures and relative configurations of 1-8 were determined by analysis of spectroscopic data, and the absolute configuration of 8 was assigned by application of the CD technique. Compounds 1, 2 and 4 were evaluated for their cytotoxic effects against P388 and A549 cells, but all were inactive. Possible biosynthetic pathways for sesquiterpenes (1-8) were discussed.     

绿槽枝衣的化学成分

从地衣绿槽枝衣( Sulcaria virens) 中分离得到一个新的亚油酸异丙叉衍生物, 通过波谱学方法包括2D-NMR 确定其化学结构为: 9, 10-O-异丙叉基- (12 Z)-十八碳烯酸(1) 。同时还得到其它12 个已知化合物:( 9 Z, 12 Z )-十八碳二烯酸(2), 扁枝衣二酸(3), ( R ) -松萝酸(4), 枕酸甲酯( 5), 黑茶渍素(6) , virensic acid ( 7), abieslactone (8), 3α-羟基羊毛甾-7, 24-二烯-26, 23 R-内酯(9), 蒲公英赛醇(10 ), 蒲公英赛酮 ( 11 ), (22 E , 24 R )-5α, 8α-过氧麦角甾-6, 22-二烯-3β-醇(12) 和2, 2′-四氢角鲨烯(13)。     

Anticonvulsants containing the N-(3-aryl-2-propenoyl) amido pharmacophore

A series of 1-(3-aryl-2-propenoyl)-4-oxopiperidines (1) as well as some related semicarbazones (2) and thiosemicarbazones (3) were prepared in order to determine whether the relative locations of aryl rings and amidic groups would lead to novel anticonvulsant agents. Initially the compounds were administered intraperitoneally to mice and examined in the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens. The biodata revealed that anticonvulsant properties were displayed by most of the compounds in series (1), in half of the semicarbazones (2) while protection was absent by members of series (3). Molecular modeling was utilized in order to compare the positions of a phenyl ring in relation to amidic groups in representative compounds in series (1-3) with previously reported anticonvulsant agents. Molecular simplification of 4-oxo-1-(3-phenyl-2-propenoyl)piperidine (la) led to 1-(3-phenyl-2-propenoyl)piperidine (7) and N,N-diethylcinnamamide (8) with retention of anticonvulsant properties. Both (la) and (8) afforded protection in the hippocampal kindling screen in rats. When administered orally to rats, (la) and (8) demonstrated activity in the MES screen and in the case of (8), a huge protection index was observed revealing it to be an important lead compound. The IC50 values of all of the compounds towards murine P388 cells were in excess of 50 microM while several compounds displayed cytotoxicity towards Mycobacterium tuberculosis.     

Prenylated flavonoids of the leaves of Macaranga conifera with inhibitory activity against cyclooxygenase-2

Two prenylated flavonoid derivatives, 5-hydroxy-4'-methoxy-2",2"-dimethylpyrano-(7,8:6",5")flavanone (1) and 5,4'-dihydroxy-[2"-(1-hydroxy-1-methylethyl)dihydrofurano]-(7,8:5",4")flavanone (2), were isolated from an ethyl acetate-soluble extract of the leaves of Macaranga conifera using an in vitro activity-guided fractionation procedure based on the inhibition of cyclooxygenase-2. Also obtained were eight known compounds, 5,7-dihydroxy-4'-methoxy-8-(3-methylbut-2-enyl)flavanone (3), lonchocarpol A (4), sophoraflavanone B (5), 5,7-dihydroxy-4'-methoxy-8-(2-hydroxy-3-methylbut-3-enyl)flavanone (6), tomentosanol D (7), lupinifolinol (8), isolicoflavonol (9), and 20-epibryonolic acid (10). The structures of compounds 1 and 2 were determined using spectroscopic methods. All isolates were tested for their inhibitory effects against both cyclooxygenases-1 and -2, and selected compounds were evaluated in a mouse mammary organ culture assay.     

Antimicrobial constituents of Scrophularia deserti

A study of the chemistry and antibacterial activity of Scrophularia deserti led to the isolation of eight compounds, including the metabolite 3(zeta)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (1). The known compounds ajugoside (2), scropolioside B (3), 6-O-alpha-L-rhamnopyranosylcatalpol (4), buddlejoside A(8) (5), scrospioside A (6), laterioside (7) and 3R-1-octan-3-yl-3-O-beta-D-glucopyranoside (8) were also isolated. Compounds 1-3 exhibited moderate antibacterial activity against strains of multidrug and methicillin-resistant Staphylococcus aureus (MRSA) and a panel of rapidly growing mycobacteria with minimum inhibitory concentration (MIC) values ranging from 32 to 128 microg/ml.     

Kinetic analysis of novel multisubstrate analogue inhibitors of thymidine phosphorylase

A kinetic analysis was performed for the novel 1-(8-phosphonooctyl)-6-amino-5-bromouracil and 1-(8-phosphonooctyl)-7-deazaxanthine inhibitors of Escherichia coli thymidine (dThd) phosphorylase (TPase). The structure of the compounds was rationally designed based on the available crystal structure coordinates of bacterial TPase. These inhibitors reversibly inhibited TPase. Kinetic analysis revealed that the compounds inhibited TPase in a purely competitive or mixed fashion not only when dThd, but also when inorganic phosphate (Pi), was used as the variable substrate. In contrast, the free bases 6-amino-5-bromouracil and 7-deazaxanthine behaved as non-competitive inhibitors of the enzyme in the presence of variable Pi concentrations while being competitive or mixed with respect to thymine as the natural substrate. Our kinetic data thus revealed that the novel 1-(8-phosphonooctyl)pyrimidine/purine derivatives are able to function as multisubstrate inhibitors of TPase, interfering at two different sites (dThd(Thy)- and phosphate-binding site) of the enzyme. To our knowledge, the described compounds represent the first type of such multisubstrate analogue inhibitors of TPase; they should be considered as lead compounds for the development of mechanistically novel type of TPase inhibitors.     

Efficacy of methylenecyclopropane analogs of nucleosides against herpesvirus replication in vitro

We have reported previously that purine methylenecyclopropane analogs are potent agents against cytomegaloviruses. In an attempt to extend the activity of these compounds, the 2-amino-6-cyclopropylaminopurine analog, QYL-1064, was selected for further study by modifying the purine 6 substituent. A total of 22 analogs were tested against herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella zoster virus (VZV), human cytomegalovirus (HCMV), murine cytomegalovirus (MCMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV-6) and human herpesvirus type 8 (HHV-8). Ten of the analogs had activity against at least one of the viruses tested. One compound had moderate activity against HSV-1 and six had activity against VZV. All but one compound was active against HCMV with a mean EC50 of 2.1 +/- 0.6 microM, compared with a mean EC50 of 3.9 +/- 0.8 microM for ganciclovir. Of special interest was the fact that eight of the ten compounds were active against both HHV-6A and HHV-6B with mean EC50 values of 6.0 +/- 5.2 mciroM and <2.4 +/- 1.5 microM, respectively. Only two compounds had activity against EBV, whereas all but one compound was active against HHV-8 with a mean EC50 of 3.1 +/- 1.7 microM. These results indicate that members of this series of methylenecyclopropane analogs are highly active against HCMV, HHV-6, and HHV-8 but are less active against HSV, VZV, and EBV.     

广东土牛膝的化学成分

广东土牛膝为菊科泽兰属植物华泽兰（Eupatorium chinense）的干燥根。从其甲醇提取物中共分离得到11个化合物,其中eupatorinA（1）为一新化合物,经波谱学方法鉴定为（threo）-3-O-acetyl-1-（4-hydroxy-3-methoxyphenyl）-2-[4-（3-hydroxy-1-（E）-propenyl）-2,6-dimethoxyphenoxy]propyl-β-D-glucopy-ranoside。已知化合物分别鉴定为（threo）-3-hydroxy-1-（4-hydroxy-3-methoxyphenyl）-2-[4-（3-hydroxy-1-（E）-propenyl）-2,6-dimethoxyphenox-y]-propyl-β-D-glucopyranoside（2）,ardisiacrispinA（3）,ardisiac-rispinB（4）,euparone（5）,3-（2,3-dihydroxy-isopen-tyl）-4-hydroxyacetophenone（6）,12,13-di-hydroxy-euparin（7）,gymnastone（8）,N-（2′-hydroxy-tetracosanosyl）-2-amino-1,3,4-trihydroxy-octa-dec-8-（E）-ene（9）,stigmasterol（10）和stigmasterol-3-O-β-D-glucopyranoside（11）。化合物2-4为首次从菊科植物,5-8为首次从泽兰属植物中分离得到。     

烟曲霉GZWMJZ-152茶粕发酵代谢产物

在茶粕培养基摇床培养条件下,烟曲霉GZWMJZ-152将茶粕中的山茶苷A (1)和山茶苷B (2)代谢为山奈酚-3-O-芸香糖苷(3);在茶粕培养基静置发酵条件下,从发酵提取物中分离得到5个化合物,分别为山奈酚(4)、(-)Chaetominine (5)、trypacidin (6)、1,2-seco-trypacidin (7)、(-)-丁香脂素(8)。测试了8个化合物的α-葡萄糖苷酶抑制活性和DPPH自由基清除活性,其中化合物1-3,5-8具有较好的α-葡萄糖苷酶抑制活性,IC₅₀值在133.9-308.6μg/mL;化合物1,4,8具有较好的自由基清除活性,IC₅₀值在0.43-5.06μg/mL。