New polyoxygenated farnesylcyclohexenones, deacetoxyyanuthone A and its hydro derivative from the marine-derived fungus Penicillium sp

New polyoxygenated farnesylcyclohexenones, 7-deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2), were isolated together with the known farnesylquinones (3, 4) from a marine isolate of the genus Penicillium. The structures of the new deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2) were assigned by spectroscopic methods, including 2D NMR and CD for the Cotton effect of alpha-epoxyketone experiments. Compounds 1 and 3 showed moderate in vitro cytotoxicity in a panel of five human tumor cell lines, and 1 also exhibited mild in vitro antibacterial activity against methicillin-resistant and multidrug-resistant Staphylococcus aureus (MIC, 50 microg/mL).     

Jadomycins derived from the assimilation and incorporation of norvaline and norleucine

Streptomyces venezuelae ISP5230 is recognized for the production of chloramphenicol and the jadomycin family of natural products. The jadomycins are angucycline natural products containing a unique oxazolone ring incorporating an amino acid present in the minimal culture media. Substitution of different amino acids results in products of varying biological activity. Analysis of cultures of S. venezuelae ISP5230 incubated with l- and d-norvaline and l- and d-norleucine indicated that only the d-configured amino acids were incorporated into the natural products. Subsequently, jadomycin DNV and jadomycin DNL were isolated and characterized (titers 4 and 9 mg L(-1), respectively). The compounds were evaluated in the National Cancer Institute cell line cancer growth inhibition and cytotoxicity screens, for antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and as DNA-cleavage agents in vitro.     

Constituents of Tritonia crocosmaeflora, I. Tricrozarin A, a novel antimicrobial naphthazarin derivative

A novel naphthazarin derivative, tricrozarin A, has been isolated from the fresh bulbs of Tritonia crocosmaeflora and was characterized as 5,8-dihydroxy-2,3-dimethoxy-6,7-methylenedioxy-1,4-naphthoquinone (2,3-dimethoxy-6,7-methylenedioxynaphthazarin). Tricrozarin A exhibits antimicrobial activity against gram-positive bacteria, fungi, and yeast in vitro and is the first tetra-oxygenated naphthazarin derivative isolated from higher plants.     

曲古菌素A对心肌缺血再灌注损伤大鼠的保护作用

目的:观察曲古菌素A(Trichostatin A,TSA)对心肌缺血再灌注损伤大鼠心肌的保护作用。方法:Wistar大鼠,随机分为6组:假手术组;模型组;阳性药组;TSA 0.05,0.1,0.2 mg.kg-13个剂量组。采用结扎冠状动脉左前降支(LAD)的方法制备大鼠心肌缺血再灌注损伤(I/R)模型,手术前连续5 d ip给药,缺血30 min再灌注24 h后观察TSA对心肌I/R模型大鼠心肌梗死面积、组织病理学及血清中超氧化物歧化酶(SOD)、丙二醛(MDA)含量的影响。结果:与模型组相比,TSA能降低心肌I/R模型大鼠心肌梗死面积,增加血清SOD活性,减少脂质过氧化物MDA含量,对I/R引起的心肌组织病理结构改变有明显改善作用。结论:TSA对缺血再灌注损伤大鼠心肌具有保护作用。     

Cytotoxic lignans of Justicia ciliata.

Two new naturally occurring 1-aryl-2,3-naphthalide lignans, cilinaphthalide A (1) and cilinaphthalide B (2), and nine known compounds were isolated from the whole plant of Justicia ciliata. Their structures were established by spectral analysis, and their cytotoxic activity was evaluated against several different cell lines. The known compound, justicidin A, showed potent cytotoxic effects against T-24, CaSki, SiHa, HT-3, PLC/PRF/5, and 212 cells in vitro.     

Seco-terpenoids and other constituents from Elateriospermum tapos

Two new taraxerane triterpenes, 2,3-seco-taraxer-14-ene-2,3,28-trioic acid 2,3-dimethyl ester ( 1) and 2,3-seco-taraxer-14-ene-2,3,28-trioic acid 3-methyl ester ( 2), along with two known triterpenes, hopenol B and aleuritolic acid, and five known flavonoids, putraflavone, kaempferol, sequoiaflavone, amentoflavone, and ginkgetin, were isolated from the leaves of Elateriospermum tapos. The stem extract yielded a new cleistanthane diterpene, 2,3-seco-sonderianol ( 3), three known triterpenes, lupeol, lupeol acetate, and 3-acetylaleuritolic acid, and three known diterpenes, yucalexin B-22, yucalexin P-15, and yucalexin P-17. The structures of these compounds were established on the basis of their spectroscopic data. Compound 1 was cytotoxic against NCI-H187 and BC cell lines and also showed in vitro antimycobacterial activity against Mycobacterium tuberculosis.     

Neamphamide A, a new HIV-inhibitory depsipeptide from the Papua New Guinea marine sponge Neamphius huxleyi

A new HIV-inhibitory cyclic depsipeptide, neamphamide A (2), was isolated from a Papua New Guinea collection of the marine sponge Neamphius huxleyi. Its structure was established through interpretation of spectroscopic data and by acid hydrolysis, derivatization of the free amino acids, and LC-MS analysis of the derivatives. Neamphamide A (2) contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethylheptanoic acid moiety. The amino acid constituents were identified as L-Leu, L-NMeGln, D-Arg, D- and L-Asn, two residues of D-allo-Thr, L-homoproline, (3S,4R)-3,4-dimethyl-L-glutamine, beta-methoxytyrosine, and 4-amino-7-guanidino-2,3-dihydroxyheptanoic acid. In a cell-based XTT assay, 2 exhibited potent cytoprotective activity against HIV-1 infection with an EC50 of approximately 28 nM.     

Isolation and synthesis of a new bioactive ellagic acid derivative from Combretum yunnanensis

A new ellagic acid derivative (1) was isolated from the branches of Combretum yunnanensis, and its structure was assigned as 4-(4' '-O-acetyl-alpha-rhamnopyranosyl)ellagic acid by analysis of its spectral data. Total synthesis of 1 was achieved by the glycosylation of 3,3'-di-O-benzylellagic acid (5) with 4-O-acetyl-2,3-di-O-benzyl-l-rhamnose (4) as a key reaction, and the absolute configuration of 1 was determined. Compound 1 showed weak inhibitory activity against the growth of various tumor cells and inhibited HIV-1 protease.     

Diversonol and blennolide derivatives from the endophytic fungus Microdiplodia sp.: absolute configuration of diversonol

Chemical investigation of the fungal strain Microdiplodia sp. isolated from the shrub Lycium intricatum led to the isolation of four new compounds: a hexahydroxanthone (2), a 2,3-dihydrochroman-4-one (3), a 7-oxoxanthone derivative (4), and a 1,4-oxazepan-7-one (5). The relative configurations of the new compounds were determined by intensive NMR investigations, notably NOESY experiments at different temperatures. The absolute configurations of the well-known fungal metabolite diversonol (1) and of other xanthone derivatives (3, 4) were established by means of TDDFT ECD calculations. Most of the metabolites were biologically active, with antibacterial activity against Legionella pneumophila and/or antifungal activity against Microbotryum violaceum.     

Antimicrobial spectrum of Alchornea cordifolia leaf extract

The 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell. Arg. leaf was screened for activity against 74 microbial strains representing aerobic, facultative and anaerobic bacteria as well as fungi. The panel of test strains included organisms from culture collections as well as clinical and environmental isolates. A concentration of 5 mg/mL of extract inhibited 36.5% of the isolates and 95.9% were inhibited by a concentration of 20 mg/mL. Only three strains, all filamentous fungi, were not susceptible to 40 mg/mL of the extract, the highest concentration tested. The extract showed the best activity against gram-positive bacteria and yeasts with inhibitory concentrations against these organisms being under 5 mg/mL. The results demonstrate that the A. cordifolia extract has a very broad spectrum of activity and suggests that it may be useful in the treatment of various microbial infections.     

Antitumor agents, 119. Kansuiphorins A and B, two novel antileukemic diterpene esters from Euphorbia kansui

The extract of the roots of Euphorbia kansui, which has been widely used in Chinese folk medicine for the treatment of cancer, demonstrated antileukemic activity against the P-388 lymphocytic leukemia in mice. Bioassay-directed fractionation of the active extract led to the isolation and characterization of two novel antileukemic diterpene esters, kansuiphorin A [1] [13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate- 20- hexadecanoate] and kansuiphorin B [2] [6,7-epoxy-13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-do decanoate-20- hexadecanoate], whose structures were established from spectral evidence and chemical transformation. Kansuiphorins A and B demonstrated potent antileukemic activity with T/C greater than or equal to 176 and 177% at 0.1 and 0.5 mg/kg, respectively. The selectivity of kansuiphorin A, which inhibits the growth of particular cell types within the disease-oriented human cancer cell line panels, is discussed.     

Sesquiterpenes and flavonol glycosides from Zingiber aromaticum and their CYP3A4 and CYP2D6 inhibitory activities

Three new sesquiterpenes, (2R,3S,5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (1), (2R,3R,5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (2), and (5R)-2,6,9-humulatrien-5-ol-8-one (3), and two new flavonol glycosides, kaempferol-3-O-(2,3-di-O-acetyl-alpha-l-rhamnopyranoside) (4) and kaempferol-3-O-(2,3,4-tri-O-acetyl-alpha-l-rhamnopyranoside) (5), were isolated from the EtOAc-soluble fraction of the water extract of Zingiber aromaticum, along with 13 known compounds (6-18). The structures of the isolated compounds were elucidated on the basis of spectroscopic and chemical analyses. The isolated compounds were tested for their inhibitory activity on the metabolism mediated by CYP3A4 or CYP2D6 using [N-methyl-(14)C]erythromycin or [O-methyl-(14)C]dextromethorphan as a substrate, respectively. Kaempferol-3-O-(2,3,4-tri-O-acetyl-alpha-l-rhamnopyranoside) (5) showed the most potent inhibitory activity (IC(50), 14.4 microM) on the metabolism mediated by CYP3A4, and kaempferol-3-O-methyl ether (14) inhibited CYP2D6 most potently (IC(50), 4.63 microM).     

Bromophenols coupled with methyl gamma-ureidobutyrate and bromophenol sulfates from the red alga Rhodomela confervoides

Four new bromophenols C-N coupled with methyl gamma-ureidobutyrate (1-4), a phenylethanol bromophenol (5), and three phenylethanol sulfate bromophenols (6-8) have been isolated from polar fractions of an ethanolic extract of the red alga Rhodomela confervoides. On the basis of spectroscopic evidence including HRMS and 2D NMR data, the structures of the new compounds were determined as methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (1), methyl N,N'-bis(2,3-dibromo-4,5-dihydroxybenzyl)-gamma-ureidobutyrate (2), methyl N'-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (3), methyl N'-(2,3-dibromo-4,5-dihydroxybenzyl)-N'-[3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxybenzyl]-gamma-ureidobutyrate (4), 2,3-dibromo-4,5-dihydroxyphenylethanol (5), 2,3-dibromo-4,5-dihydroxyphenylethanol sulfate (6), 3-bromo-4,5-dihydroxyphenylethanol sulfate (7), and 3-bromo-2-(2,3-dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxyphenylethanol sulfate (8). The cytotoxicity of all compounds was evaluated against several human cancer cell lines including human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), and human ovarian cancer (A2780). Among them, the phenylethanol and the phenylethanol sulfate bromophenols (5-8) showed moderate cytotoxicity against all tested cell lines.     

Antimicrobial isopropenyl-dihydrofuranoisoflavones from Crotalaria lachnophora

Two new isopropenyl-dihydrofuranoisoflavones exhibiting antimicrobial properties have been isolated along with eight known compounds from the Cameroonian medicinal plant Crotalaria lachnophora. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry as 7,2',4'-trihydroxy-5'-isopropenyl-4',5'-dihydrofurano[2',3':5,6]isoflavone (1) and 4,8-dihydroxy-2-isopropenyl-2,3-dihydro-5H-[1]benzofuro[2,3-b]furo[3,2-g]chromen-5-one (2). The CH(2)Cl(2)/MeOH (1:1) extract and the compounds isolated were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Gram-positive and Gram-negative bacteria and fungi. The new compounds, named lachnoisoflavones A (1) and B (2), showed moderate inhibitory activities against Escherichia coli and Klebsiella pneumoniae.     

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).     

Trichostatin analogues JBIR-109, JBIR-110, and JBIR-111 from the marine sponge-derived Streptomyces sp. RM72

Three new trichostatin analogues, JBIR-109 (1), JBIR-110 (2), and JBIR-111 (3), were isolated from the culture of the marine sponge-derived Streptomyces sp. strain RM72, together with trichostatin A (4) and trichostatic acid (5). The planar structures of 1-3 were determined on the basis of extensive NMR and MS analyses. In addition, the absolute configurations of the amino acid residues were determined by Marfey's method. The histone deacetylase inhibitory activities of 1-5 were examined, and their structure-activity relationships are discussed.     

Isolation, structure, and coccidiostat activity of coccidiostatin A

Coccidiosis is one of the more common and costly diseases in poultry that is caused by various Eimeria species. In our quest to discover coccidiostats from natural products, we discovered a microbial fermentation extract that exhibited in vivo anticoccidial activity. Fractionation of this extract led to the discovery of two potent antiprotozoals, emecorrugatin A (1) and coccidiostatin A (2). The former compound exhibited only in vitro activity, whereas the latter new compound exhibited in vivo activity against Eimeria species in chickens at 150 ppm dosed in chicken feed. The isolation, structure elucidation, relative configuration, and activity of coccidiostatin A (2) are described.     

地黄内生真菌中一个新的二苯醚类代谢产物

目的：研究地黄内生真菌的代谢产物。方法：采柱色谱方法进行分离纯化,并根据化合物的理化性质和波谱数据鉴定其结构。结果：从地黄内生真菌代谢产物中分离并鉴定了10个化合物：2,4-dihydroxy-2＇,6-diacetoxy-3＇-methoxy-5＇-methyl-diphenylether（1）,paecilospirone（2）,α-axetylorcino（3）,2-rnethoxy-1,8-dimethyl-xanthen-9-one（4）,4-hydroxy-a-lapachone（5）,enalinA（6）,2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran（7）,P-hydroxyethyl-phenol（8）,2,4-dihydroxy-3,5,6-trime-thyl-methylbenzoate（9）,3-isopropenyl-（z）-rnonomethylmaleate（IO）。结论：化合物1为新的二苯醚类化合物,其显示了一定的细胞毒和抗真菌活性。     

Induced production of N-formyl alkaloids from Aspergillus fumigatus by co-culture with Streptomyces peucetius

Co-culture of the fungus Aspergillus fumigatus with the bacteria Streptomyces peucetius led to the induction of production of formyl xanthocillin analogues. This mixed fermentation yielded two new metabolites, fumiformamide (1) and N,N'-((1Z,3Z)-1,4-bis(4-methoxyphenyl)buta-1,3-diene-2,3-diyl)diformamide (2), together with two known N-formyl derivatives and the xanthocillin analogue BU-4704. The structures were determined by spectroscopic methods and by comparison with literature. Cytotoxic activity of all the analogues was tested on the NCI-60 cell line screen, and compound 2 exhibited significant activity against several cell lines. The analogues did not show antimicrobial activity.     

A new bioactive sesterterpene and antiplasmodial alkaloids from the marine sponge hyrtios cf. erecta

From the CH(2)Cl(2) extract of the sponge Hyrtios cf. erecta, collected from Fiji, two new sesterterpenes, 1 and 2, and the known compounds isodehydroluffariellolide (3), homofascaplysin A (4), and fascaplysin (5) were isolated. The structures of 1-5 were established employing 1D and 2D NMR spectroscopy and mass spectrometry. All NMR resonances of fascaplysin (5) have been unambiguously assigned. Evaluation of the biological activity of the extracts and pure compounds toward Plasmodium falciparum, Trypanosoma brucei subsp. rhodesiense, Trypanosoma cruzi, hepatitis A virus (HAV), several other microbial targets, and HIV-1-RT and p56(lck) tyrosine kinase revealed new activities for homofascaplysin (4) and fascaplysin (5), both being potently active in vitro against P. falciparum.