青霉属真菌Penicillium sp. CPCC 400786的抗病毒活性成分

采用抗艾滋病毒抑制剂筛选模型对一株青霉属真菌Penicillium sp. CPCC 400786发酵产物的乙酸乙酯提取物进行活性评价,结果显示,其对艾滋病毒有较强的抑制活性。采用正相硅胶柱、Sephadex LH-20凝胶柱和半制备HPLC等色谱技术对乙酸乙酯提取物进行分离纯化,从中分离得到8个化合物。通过波谱数据分析,分别鉴定为：oxalicine A（1）、oxalicine B（2）、cis-4,6-dihydroxymellein（3）、亚油酸（4）、十八烯酸（5）、肉豆蔻酸（6）、尿嘧啶（7）、胸腺嘧啶（8）。化合物1和2为杂萜类化合物。对化合物1-6进行了抗艾滋病毒（HIV-1）和抗甲型流感病毒（H1N1）的活性评价。结果显示,化合物1具有良好的抗H1N1活性,其IC₅₀值为38.5μmol/L,比阳性对照药利巴韦林稍弱（IC₅₀=20.5μmol/L）;化合物1和2具有抗HIV-1的活性,其IC₅₀值分别为22.4、67.8μmol/L;其他化合物未显示抗病毒活性。本研究为从青霉属中发现更多抗病毒活性杂萜分子提供了依据。     

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.     

青灰叶下珠内生菌Phomopsis sp.TJ507A的化学成分及生物活性研究

为探究药用植物青灰叶下珠(Phyllanthus glaucus)来源内生真菌拟茎点霉(Phomopsis sp. TJ507A)的化学成分,本实验联合运用硅胶柱色谱、ODS柱色谱、凝胶柱色谱(Sephadex LH-20)、半制备型高效液相色谱(HPLC)等分离技术,从该菌株大米固体发酵产物的乙酸乙酯提取物中分离得到4个倍半萜化合物phomophyllin O(1)、phomophyllin P(2)、7-hydroxy-10-methoxydehydrodihydrobotrydial(3)、plorantinone D(4)和8个甾体化合物fortis-terol(5)、dankasterone B(6)、(14α,22E)-14-hydroxy-ergosta-7,22-diene-3,6-dione(7)、(14α,22E)-14-hydroxyerg-osta-4,7,22-triene-3,6-dione(8)、calvasterol B(9)、isocyathisterol(10)、ergosta-4,6,8(14),22-tetraen-3-one(11)和ganodermaside D(12)。化合物1和2为新化合物,运用现代波谱分析技术、[Rh2(OCOCF3)4]络合诱导ECD法及与文献对比等方法,鉴定了化合物1和2的结构和绝对构型。化合物1～5、7、8和10均为首次从该属真菌中分离得到。通过体外生物活性评价,发现化合物9具较强的NO生成抑制活性(IC508. 7μM)。     

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.     

Molecular and crystal structures of N-aryl-beta-D-glycopyranosylamines from mannose and galactose.

The molecular and crystal structures of 12 N-aryl-beta-D-glycopyranosylamines have been determined by X-ray crystallography. Six of these are mannose derivatives, the N-p-bromophenyl (1), N-p-tolyl (2), N-m-chlorophenyl (3), N-p-methoxyphenyl (4), N-o-chlorophenyl (5), and N-o-tolyl (6) derivatives that are formed by reaction with the corresponding substituted anilines. The remaining six are galactose derivatives, the N-phenyl (7), N-p-chlorophenyl (8), N-p-bromophenyl (9), N-p-iodophenyl (10), N-p-nitrophenyl (11) and N-p-tolyl (12), derivatives prepared similarly. Compounds 1-3 assume the same packing arrangement. Compounds 4, 5, and 6 assume unique packing arrangements, although that assumed by 4 is closely related to that assumed by 1-3. Compounds 7-11 assume the same packing arrangement; that assumed by 12 is closely related to that assumed by 7-11. That the same packing arrangements can be maintained in spite of substantial changes in the electronic and steric nature of the substituent on the aryl ring reflects the strength of the hydrogen bond network connecting the monosaccharide portions of the molecules in the solid state. A hydrogen bonding motif found in all six mannose structures is a mutual interaction between translationally related molecules involving O-3-H...O-5 and O-6-H...O-4 hydrogen bonds. The recurrence of this motif throughout this group of mannosylamines suggests that it is an especially favorable interaction that might be expected to occur also in related macromolecular systems.     

New production of 5-bromotoluhydroquinone and 4-O-methyltoluhydroquinone from the marine-derived fungus Dothideomycete sp

The addition of NaBr to the fermentation medium of a marine isolate of the fungus Dothideomycete sp. resulted in induced production of two toluhydroquinone derivatives, 5- bromotoluhydroquinone (1) and 4-O-methyltoluhydroquinone (2), and two known compounds, toluhydroquinone (3) and gentisyl alcohol (4). The structures of 1 and 2 were assigned through the spectroscopic data analyses. Compounds 1-4 showed a potent antibacterial activity against the methicillinresistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA) with MIC (minimum inhibitory concentration) values of 6.2, 12.5, 6.2, and 12.5 microgram/ml, respectively. Compounds 1-4 also exhibited a moderate radical scavenging activity against 1,1-diphenyl-2- picrylhydrazyl (DPPH) with IC(50) values of 11.0, 17.0, 12.0, and 7.0 microM, respectively, which were more active than the positive control, L-ascorbic acid (IC(50), 20.0 μM).     

Antifeedant and phytotoxic activity of cacalolides and eremophilanolides

The antifeedant effect of six cacalolides and six eremophilanolides was tested against the herbivorous insects Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. The test compounds included several natural products isolated from Senecio madagascariensis (14-isovaleryloxy-1,2-dehydrocacalol methyl ether, 4), S. barba-johannis (13-hydroxy-14-oxocacalohastine, 5; 13-acetyloxy-14-oxocacalohastine, 6) and S. toluccanus [6-hydroxyeuryopsin, 7; 1(10)-epoxy-6-hydroxyeuryopsin, 9; toluccanolide A, 11] and the derivatives cacalol methyl ether (1); cacalol acetate (2); 1-acetyloxy-2-methyloxy-1,2,3,4-tetradehydrocacalol acetate (3); 6-acetyloxyeuryopsin (8); 6-acetyloxy-1(10)-epoxyeuryopsin (10), and toluccanolide A acetate (12). Compound 11 and its derivative 12 exhibited moderate antifeedant activity against S. littoralis; 2, 7-10, and 12 showed strong activity against L. decemlineata, while the aphid M. persicae was moderately deterred in the presence of compounds 1, 4, 8, 10, and 12. The phytotoxic activity of 1-12 on Lactuca sativa was also evaluated. Compounds 2 and 4-12 moderately inhibited seed germination at 24 h, while compounds 1-4, 6, 9, and 10 had a significant inhibition effect on L. sativa radicle length (over 50%).     

绿僵菌SC0924含氮杂环类代谢产物及其抗荔枝霜疫霉活性

从绿僵菌(Metarhizium sp.SC0924)固体发酵物中分离得到12个含氮杂环类化合物,通过波谱分析,分别鉴定为环(丙氨酸-脯氨酸)(1)、环(脯氨酸-酪氨酸)(2)、环(缬氨酸-亮氨酸)(3)、环(亮氨酸-异亮氨酸)(4)、腺嘌呤(5)、腺嘌呤核苷(6)、尿嘧啶(7)、胸腺嘧啶(8)、胸腺嘧啶脱氧核苷(9)、4-乙酰氨基咪唑(10)、焦谷氨酸正丁酯(11)和光敏素(12).滤纸片琼脂扩散法试验表明化合物2和3具有较弱的抗荔枝霜疫霉活性.     

海洋真菌Arthrinium sp. UJNMF0008代谢产物的研究

为丰富海洋真菌的化学多样性,发现海洋真菌活性代谢产物,对海洋沉积物来源真菌Arthriniumsp.UJNMF0008的化学成分及其生物活性进行研究,采用硅胶柱色谱、凝胶柱色谱、反向柱色谱和高效液相色谱等方法从海洋沉积物来源真菌Arthriniumsp.UJNMF0008的发酵提取物中分离到5个化合物,通过核磁共振、质谱等方法,结合文献对照,鉴定了化合物的结构分别为arthoneF(1)、arthoneG(2)、sydoxanthoneC(3)、(3R,4R)-cis-4-hydroxymellein(4)和2-(2′S-hydroxypropyl)-5-methyl-7-hydroxychromone(5),其中化合物1和2是新化合物,化合物3首次从该属真菌中分离到。活性测试显示,化合物1~5在50μmoL/L的测试浓度下均没有表现出明显的抗氧自由基活性、抗菌活性以及NO释放抑制活性。     

Novel terpenoids of the fungus Aspergillus insuetus isolated from the Mediterranean sponge Psammocinia sp. collected along the coast of Israel

Three novel meroterpenoids, insuetolides A-C (1-3) and four drimane sesquiterpenes, the new (E)-6-(4'-hydroxy-2'-butenoyl)-strobilactone A (4) and the known 2α, 9α, 11-trihydroxy-6-oxodrim-7-ene (5), strobilactone A (6) and (E,E)-6-(6',7'-dihydroxy-2',4'-octadienoyl)-strobilactone A (7), were isolated from the EtOAc extract of the culture medium of the marine-derived fungus Aspergillus insuetus (OY-207), which was isolated from the Mediterranean sponge Psammocinia sp. The structures of the compounds were determined by spectroscopic methods. Insuetolides A-C reveal a new carbon skeleton derived from the cyclization of farnesyl and 3, 5-dimethylorsellinic acid. Compounds 1, 6, and 7 exhibited anti-fungal activity towards Neurospora crassa with MIC values of 140, 242, and 162 μM, respectively; and compounds 3, 4, and 7 exhibited mild cytotoxicity towards MOLT-4 human leukemia cells.     

Diverse secondary metabolites produced by marine-derived fungus Nigrospora sp. MA75 on various culture media

Bioassay-guided isolation of a fungal strain Nigrospora sp. MA75, an endophytic fungus obtained from the marine semi-mangrove plant Pongamia pinnata, which was fermented on three different culture media, resulted in the isolation and identification of seven known compounds, 2, 3, and 5-9, from a medium containing 3.5% NaCl, while a new compound, 2,3-didehydro-19α-hydroxy-14-epicochlioquinone B (10) was obtained from the medium containing 3.5% NaI. In addition, two new griseofulvin derivatives, 6-O-desmethyldechlorogriseofulvin (1) and 6'-hydroxygriseofulvin (4), were isolated and identified from the rice solid medium. Dechlorogriseofulvin (2) and griseofulvin (3) were the major components in fermentation extracts of all these culture media, while compounds 1 and 4, 5 and 6, and 10 were only present in the extract of respective culture medium. The structures of these compounds were elucidated by detailed spectroscopic analysis, and the absolute configuration of 1 was determined by CD measurement. Compounds 9 and 10 exhibited antibacterial activities toward five tested bacterial strains, while compounds 5, 6, and 8 selectively inhibited MRSA, E. coli, and S. epidermidis, and compound 3 showed moderate activity against V. mali and S. solani. Moreover, compound 10 potently inhibited the growth of MCF-7, SW1990, and SMMC7721 tumor cell lines with IC(50) values of 4, 5, and 7 μg/ml, respectively.     

齿菌子实体的化学成分研究

利用硅胶柱层析和Sephadex LH-20凝胶柱层析分离手段,从高等真菌齿菌(Hydnellumsp.No.2)子实体的甲醇提取物中分离鉴定了7个化合物,经现代光谱学技术鉴定为麦角甾-7,22-二烯-3β-醇(1)、5α,8α-过氧麦角甾-6,22-二烯-3β-醇(2)、(22E,24R)-3β-羟基-24-甲基胆甾-5,22-二烯-7-酮(3)、对羟基苯甲酸甲酯(4)、(24R)-麦角甾-7,22-二烯-3β,5α,6β-三醇(5)、Tuberoside(6)和脑苷脂B(7)。化合物4、5、6、7为该属首次报道。     

Halenaquinone and xestoquinone derivatives, inhibitors of Cdc25B phosphatase from a Xestospongia sp

Separation of an extract of a Xestospongia sp., guided by bioassay against Cdc25B, led to the isolation of nine compounds, halenaquinone (1), xestoquinone (2), adociaquinones A (3) and B (4), 3-ketoadociaquinones A (5) and B (6), tetrahydrohalenaquinones A (7) and B (8), and 13-O-methyl xestoquinol sulfate (9). The structures of the new natural products 6 and 9 were established on the basis of extensive one- and two-dimensional NMR studies. Compounds 1, 4, and 6 inhibited recombinant human Cdc25B in vitro with IC50 values of 0.7, 0.07, and 0.2 microM, respectively, and were 19- to 150-fold less active against two related protein phosphatases. Compound 4 blocked cell cycle progression through mitosis.     

Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves

Ayurvedic medicines prepared in India consist of Withania somnifera roots as one of the main ingredients. It is consumed as a dietary supplement around the world. The leaves of W. somnifera were used in the treatment of tumors and inflammation in several Asian countries. We have isolated twelve withanolides such as withaferin A (1), sitoindoside IX (2), 4-(1-hydroxy-2, 2-dimethylcyclpropanone)-2, 3-dihydrowithaferin A (3), 2, 3-dihydrowithaferin A (4), 24, 25-dihydro-27-desoxywithaferin A (5), physagulin D (1-->6)-beta-D-glucopyranosyl- (1-->4)-beta-D-glucopyranoside (6), 27-O-beta-D-glucopyranosylphysagulin D (7), physagulin D (8), withanoside IV (9), and 27-O-beta-D-glucopyranosylviscosalactone B (10), 4, 16-dihydroxy-5beta, 6beta-epoxyphysagulin D (11), viscosalactone B (12) from the leaves of this species. Compounds 1-12 and diacetylwithaferin A (13) were tested for their antiproliferative activity on NCI-H460 (Lung), HCT-116 (Colon), SF-268 (Central Nervous System; CNS and MCF-7 (Breast) human tumor cell lines. The inhibitory concentration to afford 50% cell viability (IC50) for these compounds was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Withaferin A and its derivatives exhibited inhibitory concentrations (50%) ranging from 0.24 +/- 0.01 to 11.6 +/- 1.9 microg/mL. Viscosalactone B (12) showed the 50% inhibition at concentrations ranging from 0.32 +/- 0.05 to 0.47 +/- 0.15 microg/mL whereas its 27-O-glucoside derivative (10) exhibited IC50 between 7.9 +/- 2.9 and 17.3 +/- 3.9 microg/ml. However, Physagulin D type withanolides showed either weak or no activity at 30 microg/mL. Therefore, incorporation of withanolides in the diet may prevent or decrease the growth of tumors in human.     

Three New Hydroxyphenylacetic Acid Derivatives and A New Alkaloid from Endophytic Fungus Mortierella sp. in Epimedium acuminatum Franch. and Their Antibacterial Activity

Three new hydroxyphenylacetic acid derivatives, stachylines E-G ( 1 – 3 ), and a new alkaloid, mortieridinone ( 4 ), along with six known compounds ( 5 – 10 ), were isolated from endophytic fungus Mortierella sp. in Epimedium acuminatum Franch. Their structures were determined by their spectroscopic analyses and by comparison with the literature data. Compounds 7 and 10 showed selective antibacterial activity against tested multidrug-resistant bacteria with minimum inhibitory concentration (MIC) values ranging from 25 to 3.13 μg/mL.     

Desulfohaplosamate, a new phosphate-containing steroid from Dasychalina sp., is a selective cannabinoid CB2 receptor ligand

From the polar organic extract of the Indonesian sponge Dasychalina sp. we have isolated haplosamate A (1), a unique C(28) sterol containing a sulfate group at C-3 and a methyl phosphate at C-15, along with its new desulfo analogue 2, whose structure has been secured by detailed NMR investigation. Compounds 1 and 2, as well as their semi-synthetic analogues 3-5, have been evaluated for interaction with CB(1) and CB(2) receptors through a binding test. Desulfohaplosamate (2) showed a selective affinity for CB(2) receptors in the low μM range, while a semi-synthetic derivative with cleaved ring B showed a complete loss of affinity for both receptors, highlighting the importance of an intact steroid nucleus. To our knowledge, haplosamate derivatives represent the first CB receptor ligands belonging to the class of steroids.     

栓菌Trametes sp. G048的化学成分研究

从栓菌属真菌Trametes sp. G048的发酵液和菌丝体中分离并鉴定出6个化合物,经波谱数据分析分别鉴定为isodrimenediol diacetate(1)i、sodrimenediol 2-acetate(2)、脑苷脂D(3)、麦角甾醇(4)、过氧化麦角甾醇(5)和啤酒甾醇(6)。其中化合物1和2为新的天然产物。     

Two novel C29-5beta-sterols from the stems of Opuntia dillenii

Two novel C29-5beta-sterols, opuntisterol [(24R)-24-ethyl-5beta-cholest-9-ene-6beta,12alpha-diol] (1) and opuntisteroside [(24R)-24-ethyl-6beta-[(beta-d-glucopyranosyl)oxy]-5beta-cholest-9-ene-12alpha-ol] (2), together with nine known compounds, beta-sitosterol (3), taraxerol (4), friedelin (5), methyl linoleate (6), 7-oxositosterol (7), 6beta-hydroxystigmast-4-ene-3-one (8), daucosterol (9), methyl eucomate (10) and eucomic acid (11), were isolated from the stems of Opuntia dillenii collected in Guizhou Province, China. Their structures were elucidated mainly by spectroscopic analysis. The absolute configuration of 1 were deduced from comparative 1H NMR data of the (S)- and (R)-methoxyphenyl acetate derivatives. Compounds 6-8, 10 and 11 were isolated from O. dillenii for the first time.     

源自海洋裸孢壳属真菌Emericella sp. TJ414JZ-21的次级代谢产物

采用硅胶柱层析、中压反相柱层析、Sephadex LH-20凝胶柱层析以及半制备高效液相色谱等分离技术,从真菌Emericella sp.的大米发酵产物中分离得到了8个单体化合物,并利用波谱学方法结合文献数据对其结构进行了鉴定,分别为：asteltoxin (1)、asteltoxin B (2)、penicillide (3)、purpactin A (4)、tajixanthone hydrate (5)、mycophenolic acid (6)、trans-dehydrodiferulate dimethyl ester (7)、2,8-dihydroxy-1,3-dimethoxy-6-methylanthraquinone (8)。其中,化合物3和4均为首次从该属真菌中分离得到。     

Novel tacrine derivatives that block neuronal calcium channels

A new series of tacrine (9-amino-1,2,3,4-tetrahydroacridine) derivatives were synthesized and their effects on 45Ca(2+) entry into bovine adrenal chromaffin cells stimulated with dimethylphenylpiperazinium (DMPP) or K(+), studied. At 3 microM, compound 1 did not affect (45)Ca(2+) uptake evoked by DMPP. Compounds 14, 15 and 17 inhibited the effects of DMPP by 30%. Compounds 3, 9 and tacrine blocked the DMPP signal by about 50%. Compounds 5 and 12 were the most potent blockers of DMPP-stimulated 45Ca(2+) entry (90%); the rest of the compounds inhibited the effects of DMPP by 70-80%. Compounds 1, 3, 4, 8, 10, 11, 13, 16, 17 and tacrine inhibited 45Ca(2+) uptake induced by K(+) about 20%. Compounds 6, 14 and 15 inhibited the K(+) effects by 10% or less. Compounds 7, 9, 12 and 18 blocked the K(+) signal by 30% and, finally, compounds 2 and 5 inhibited the K(+)-induced 45Ca(2+) entry by 50%. None of the new compounds was as effective as diltiazem (IC(50)=0.03 microM) in causing relaxation of the rat aorta precontracted with 35 mM K(+); the most potent was compound 7 (IC(50)=0.3 microM). Compounds 5, 6, 8, 9, 10 and 13 had IC(50)s around 10 microM and compounds 3, 4, 11 and 12 around 20 microM. Blockade of Ca(2+) entry through neuronal voltage-dependent Ca(2+) channels, without concomitant blockade of vascular Ca(2+) channels, suggests that some of these compounds might exhibit neuroprotectant effects but not undesirable hemodynamic effects.