Bioactive coumarin derivatives from the fern Cyclosorus interruptus

Three new coumarin derivatives, compounds 1-3, three new furanocoumarins, compounds 4-6, and a novel dioxocane derivative, compound 7, were isolated from the fern Cyclosorus interruptus (Willd.) H. It?. Based on spectrometric and spectroscopic analysis (FAB or El mass spectrometry as well as 1D and 2D NMR experiments) their structures were characterised as 5,7-dihydroxy-6-methyl-4-phenyl-8-(3-phenylpropionyl)-1-benzopyran-2-one (1), 5,7-dihydroxy-6-methyl-4-phenyl-8-(3-phenyl-trans-acryloyl)-1- benzopyran-2-one (2), 5,7-dihydroxy-8-(2-hydroxy-3-phenylpropionyl)-6-methyl-4-phenyl-1- benzopyran-2-one (3), 8-benzyl-5,8-dihydroxy-6-methyl-4-phenylfuro[2,3-h]-1-benzopyran-2,9- dione (4), 8-benzyl-5,8 beta,9 beta-trihydroxy-6-methyl-4-phenyl-8,9-dihydro- furo[2,3-h]-1-benzopyran-2-one (5), 8-benzyl-5,8 beta,9 alpha-trihydroxy-6-methyl-4-phenyl-8,9-dihydro- furo[2,3-h]-1-benzopyran-2-one (6) and 5,11-dihydroxy-6-methyl-4-phenyl-11-(1-phenylmethyl)-7,10-dioxocane [5,6-h]-1-benzopyran-2,12-dione (7). For these compounds we propose the trivial names interruptins A-F. Compounds 1, 5/6 and 7 showed antibacterial activity while compounds 1 and 2 were cytotoxic to a KB cell line.     

包瑞弯孢菌C. borreriae HS-FG-237次级代谢产物及其生物活性研究

目的 研究包瑞弯孢菌(Curvularia borreriae)HS-FG-237菌株的次级代谢产物及其生物活性。方法 采用HP-20树脂柱、硅胶柱层析、Sephadex LH-20凝胶柱层析、半制备高效液相分析等色谱分离手段对菌体发酵液进行分离与纯化,同时利用现代波谱分析技术鉴定所得化合物结构;以3种肿瘤细胞A549,K562和MDA-MB-231为供试细胞株,采用CCK-8法对分离得到化合物进行细胞毒性研究。结果 从C. borreriae HS-FG-237菌株发酵液提取物中获得12个代谢产物,分别鉴定为：curvalarol A (1), 3β,12β-dihydroxy-4,4,14α-trimethyl-5α-pregna-7,9(11)-diene-20s-carboxylate (2), curva larol B (3), 3β-Hydroxy-lanost-24-en (4), cyclo-(Gly-Pro) (5), cyclo-(Pho-Thr) (6), cyclo-(Leu-Pro) (7), 4,6,8-Trihydroxy-2,3-dihydro-2H-naphthalen-1-one (8), cyclo-(4-hydroxyl-Pro-Leu) (9), ergosterolperoxide (10), 9-β-D-ribofuranosyl adenine (11), cerebr oside C (12),均为已知化合物;生物活性结果显示化合物1~3和10对3种肿瘤细胞有一定的细胞毒活性。结论 环二肽化合物为C. borreriae HS-FG-237菌株的主要代谢产物,12个化合物均为首次从该菌中分离得到。     

Antiproliferative constituents in plants 14. Coumarins and acridone alkaloids from Boenninghausenia japonica NAKAI

The MeOH extracts of the ground part and the root of Boenninghausenia japonica NAKAI showed inhibitory activity against tumor cell growth. Fractionation of the extracts has resulted in isolation of 1,3-dihydroxy-4-(2'-hydroxy-3'-hydroxymethyl-3',4'-epoxy-butyl)-N-methylacridone, 1,3-dihydroxy-4-[(Z)-3'-hydroxy-3'-methyl-buten-1'-yl]-N-methylacridone, 3-(1',1'-dimethylallyl)-7-hydroxy-8-methoxy-2H-1-benzopyran-2-one, casegravol, cis-casegravol, and edgeworin in addition to 9 compounds reported from B. japonica and B. albiflora. The isolates from this plant and some related compounds were tested for antiproliferative activity against human gastric adenocarcinoma (MK-1), human uterus carcinoma (HeLa), and murine melanoma (B16F10) cells.     

Norlignans from Pouzolzia zeylanica var. microphylla and their nitric oxide inhibitory activity

Five new compounds, pouzolignan F [4-hydroxy-3-(3,5-dihydroxyphenyl)-2-[bis(4-hydroxy-3-methoxyphenyl)methyl]butyl acetate] (1), pouzolignan G [4-hydroxy-3-(3,5-dihydroxyphenyl)-2-[(4-hydroxy-3,5-dimethoxyphenyl)(4-hydroxy-3-methoxyphenyl)methyl]butyl acetate] (2), pouzolignan H [1,4-dihydroxy-3-(3,5-dihydroxyphenyl)-2-[bis(4-hydroxy-3-methoxyphenyl)methyl]butane] (3), pouzolignan I [1,4-dihydroxy-3-(3,5-dihydroxyphenyl)-2-[(4-hydroxy-3,5-dime thoxyphenyl)-(4-hydroxy-3-methoxyphenyl)methyl]butane] (4), and pouzolignan J [1,4-dihydroxy-3-(3,5-dihydroxyphenyl) -2-[(3,4,5-trimethoxyphenyl)(4-hydroxy-3-methoxyphenyl)methyl]butane] (5), along with two known compounds, indolyl-3-carboxylic acid (6) and uracil (7), were isolated from the aerial parts of Pouzolzia zeylanica (L.) Benn. var. microphylla (Wedd.) W.T.Wang. The structures of these compounds were characterized based on spectroscopic methods, including IR, NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY), and HR-ESI/TOF-MS experiments. All the new norlignans were assayed for inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.     

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.     

Antitubercular constituents of Valeriana laxiflora

Antitubercular bioassay-guided fractionation of the n-hexane- and CH (2)Cl (2)-soluble extracts of the above-ground biomass and roots of Valeriana laxiflora led to the isolation of a new iridolactone, (4R,5R,7S,8S,9S)-7-hydroxy-8-hydroxymethyl-4-methyl-perhydrocyclopenta[ c]pyran-1-one ( 1), and a new lignan, (+)-1-hydroxy-2,6-bis- epi-pinoresinol ( 2), along with eleven known compounds, betulin ( 3), betulinic acid ( 4), 5,7-dihydroxy-3,6,4'-trimethoxyflavone ( 5), 23-hydroxyursolic acid ( 6), oleanolic acid ( 7), tricin ( 8), ursolic acid ( 9), ferulic acid, (+)-1-hydroxypinoresinol, prinsepiol, and 5,7,3'-trihydroxy-4'-methoxyflavone. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic evidence. The absolute stereochemistry of 1 was determined by chemical transformations and Mosher ester procedures. In a microplate alamar blue assay against Mycobacterium tuberculosis, compounds 2 - 9 exhibited minimum inhibitory concentrations (MIC) of 15.5 - 127 microg/mL, while the other isolates were regarded as inactive (MIC > 128 microg/mL). In addition, all the isolates were tested for cytotoxicity against African green monkey Vero cells in order to evaluate their selectivity potential.     

Novel polyketide metabolites from Streptomyces rimosus mutant strain R1059

Three novel polyketide metabolites were isolated from laboratory-scale fermentation of the Streptomyces rimosus mutant strain R1059. Structural elucidation of the compounds was based on NMR experiments. The compounds were characterized as naphthalene derivatives: (rel)-4beta,8-dihydroxy-3alpha-hydroxymethyl-4alpha-methyl-1,2,3,4-tetrahydronaphthalene1-one (1), 4xi8-dihydroxy-3-hydroxymethyl-4xi-methyl-1,4-dihydronaphthalene-1-one (2) and (rel)-4beta,8-dihydroxy-3alpha-O-[alpha-glucopyranosyl]hydroxymethyl-4alpha-methyl-1,2,3,4-tetrahydronaphthalene-1-one (3). The compounds isolated appear to be derived via a shorter polyketide backbone than oxytetracycline (4), the normal end-product made by the parent of this strain. Compound 3 was the glucoside of 1 and must be formed as a post-PKS reaction by the activation of a glycosyl transferase, which has not been reported in this species before.     

Five new compounds from Dendrobium longicornu

A novel bibenzyl, a new bibenzyl, two new phenanthrenes, and a new lignin glycoside, namely longicornuol A (1), 4-[2-(3-hdroxyphenol)-1-methoxyethyl]-2,6-dimethoxyphenol (2), 5-hydroxy-7-methoxy-9,10-dihydrophenanthrene-1,4-dione (3), 7-methoxy-9,10-dihydrophenanthrene-2,4,5-triol (4) and erythro-1-(4-O-beta-D-glucopyranosyl-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol ( 5), together with 14 known compounds, were isolated from the stems of Dendrobium longicornu. All structures were elucidated by spectroscopic methods (NMR, MS, UV and IR). Anti-platelet aggregation activities of compounds 1 - 5 were also tested.     

Cytotoxic steroids from Sarcococca saligna

Two new C??-steroidal esters, sarsaligates A(1) and B(2), and two new steroidal alkaloids, sarsaligenines A(3) and B(4), together with four known compounds (sarcovagine, sarcorucinine, dimethylamino-3 β-pregnane-20-one, and β-sitosterol 5- 8, respectively), were isolated from the leaves and stems of Sarcococca saligna. The structures of compounds 1-4 were elucidated by NMR and MS spectroscopic analysis. Of the compounds tested, 5 and 6 were the most cytotoxic against the cell lines K562, SK-BR-3, and PANC-1, with IC?? values in the range of 2.25-5.00?μM, while 3 and 4 selectively inhibited HL-60 cells with IC?? values of 2.87 and 3.61 μM, respectively. Compounds 3-6 therefore deserve further evaluation of their cytotoxic potentials.     

Syntheses and biological activities of 3'-azido disaccharide analogues of daunorubicin against drug-resistant leukemia

Anthracyclines, such as daunorubicin (DNR) and doxorubicin (Dox), are widely used for cancer therapy but are limited by drug resistance and cardiotoxicity. To overcome drug resistance, we synthesized a novel class of disaccharide analogues of DNR against drug-resistant leukemia. In these disaccharide analogues (1-6) the first (inner) sugar in the carbohydrate chain is a 3-azido-2,3,6-trideoxy-L-lyxo-alpha-hexopyranose; the second (outer) sugars that are linked via alpha(1-->4) to the first sugar are a series of uncommon sugars. Their cytotoxicities were examined in drug-sensitive leukemia cells K562 and doxorubicin-resistant K562/Dox cells by MTS assay. In drug-sensitive cells, compounds 1-6 were found to be active against leukemia K562 cells with IC50 in the nanomolar range (200-1100 nM), while compounds 2-5 with 2,6-dideoxy sugars showed better activity than compounds 1 and 6 with 2,3,6-trideoxy sugars. In doxorubicin-resistant K562/Dox cells, compounds 1, 3, and 5 exhibited much better activities (with IC50 between 0.29 and 2.0 microM) than DNR (with IC50 > 5 microM). Compound 3 emerged as the most active compound, showing at least 17-fold higher activity against drug-resistant cells than parent compound DNR. The IC50 values of compound 3 in both drug-sensitive and drug-resistant cells are identical, which indicates that compound 3 completely overcomes drug resistance. Structure-activity relationship (SAR) studies showed that the substitution and orientation of the 3-OH group in the second sugar significantly influence its activity against drug-resistant leukemia. These results suggest that sugar modifications of anthracyclines change their activity and overcome drug resistance.     

DNA methyltransferase inhibitor dramatically alters the secondary metabolism of Pestalotiopsis microspora

5-Azacytidine, a DNA methyltransferase inhibitor, led to significant changes in the secondary metabolism of the plant endophytic fungus, Pestalotiopsis microspora. Analysis of the culture broth extract led to the isolation of a new compound, 4′-formamidophenyl-5-methoxybenzoate (1), along with seven known polyketides, 4-hydroxybenzoic acid (2), LL-P880α (3), 1′-hydroxy-4-methoxy-6-pentyl-2H-pyran-2-one (4), pestalotiollide B (5), pestalotiopyrone G (6), endocrocin (7) and 2′-hydroxy-6′-hydroxymethyl-4′-methylphenyl-2,6-dihydroxy-3-(2-isopentenyl)benzoate (8). HPLC profiles revealed that all compounds except for 4 belonged to the newly induced secondary metabolites. In addition, all compounds were proved to be devoid of significant antifungal activity in the bioassays.     

New monoterpenes from Mentha microphylla

Four new monoterpenes, (1 R*,2 S*)-1,2-dihydroxy- p-menth-4(8)-en-3-one ( 1), (4 S*)-4-hydroxy- p-mentha-1,8-dien-3-one ( 2), (4 S*)-4-methoxy- p-mentha-1,8-dien-3-one ( 3), and (3 R*,4 R*,6 S*)-3-acetoxy-6-hydroxy- p-mentha-1,8-diene ( 4) together with four known compounds have been isolated from the aerial parts of Mentha microphylla. The structures were determined using spectroscopic methods particularly high resolution (1)H-, (13)C-NMR as well as 2D (1)H- (1)H COSY, HMQC and HMBC analysis.     

杜仲叶中倍半萜及降碳倍半萜的分离与鉴定

目的 研究植物杜仲(Eucommia ulmoides Oliver)叶中的化学成分.方法 综合运用硅胶柱色谱、反相硅胶柱色谱和Sephadex LH-20凝胶柱色谱以及制备型高效液相色谱等方法进行系统分离,根据化合物的理化性质及其波谱数据确定化合物的结构.结果 从杜仲叶80％(体积分数)乙醇提取物中分离得到了12个倍...     

New aromatic glucosides from Carthamus tinctorius

Three new aromatic glucosides, 2,3-dimethoxy-5-methylphenyl-1-O-beta-d-glucopyranoside (1), 2,6-dimethoxy-4-methylphenyl-1-O-beta-d-glucopyranoside (2), and ethyl-3-(4-O-beta-d-glucopyranosyl-3-methoxyphenyl)propionate (3), named as carthamosides B1, B2, and B3, respectively, along with three known aromatic glucosides, methyl-3-(4-O-beta-D-glucopyranosyl-3-methoxyphenyl)propionate (4), ethylsyringin (5), and methylsyringin (6), have been isolated from the air-dried flower of Carthamus tinctorius. Their structures were identified on the basis of chemical and spectroscopic methods.     

Tarennane and tarennone, two novel chalcone constituents from Tarenna attenuata

Two novel chalcone constituents, tarennane (1) and tarennone (2), together with nine known compounds, were isolated from the whole plant of Tarenna attenuata. By analysis of physical and spectroscopic data, the structures of new compounds were elucidated as (E)-4-[3-(4-hydroxy-3-methoxyphenyl)-acryl]-3,4,5-trimethoxycyclohexa-2,5-dienone (1) and 1,2-bis(3,5-dimethoxy-4-hydroxyphenyl)-3-hydroxypropan-1-one (2). These two compounds were tested for antioxidant activities in the MTT and DPPH assays. Compound 1 revealed potent antioxidant activities against H2O2-induced impairment in PC12 cells, but neither of them showed DPPH radical-scavenging activity with IC50 values of 181.1 and 210.3 microM, respectively.     

地骨皮化学成分研究

目的研究地骨皮Lycium chinense的化学成分。方法采用硅胶柱色谱法结合制备高效液相进行分离和纯化,根据理化性质和波谱数据进行结构鉴定。结果分离得到8个化合物,即saikolignanoside A(1),东莨菪苷(scopolin,2),阿魏酸(ferulic acid,3),4-羟基苯甲酸(4-hydroxy-benzoic acid,4),3-羟基-1-(3-甲氧基-4-羟基-苯基)-丙基-1-酮(3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one,5),反式-N-咖啡酰酪胺(trans-N-caffeoyltyramine,6),反式-N-阿魏酰酪胺(trans-N-feruloyltyramine,7),二氢咖啡酰酪胺(dihydro-N-caffeoyltyramine,8)。结论化合物1,5,7为首次从该属植物中分离得到。     

Two new compounds and anti-HIV active constituents from Illicium verum

Two new compounds named illiverin A (1) and tashironin A (8) were isolated from the roots of Illicium verum, together with seven known compounds: 4-allyl-2-(3-methylbut-2-enyl)-1,6-methylenedioxybenzene-3-ol (2), illicinole (3), 3-hydroxy-4,5-methylenedioxyallyl-benzene (4), (-)-illicinone-A (5), 4-allyl-4-(3-methylbut-2-enyl)-1,2-methylenedioxycyclohexa-2,6-dien-5-one (6), 3,4-seco-(24 Z)- cycloart-4(28),24-diene-3,26-dioic acid, 26-methyl ester (7) and tashironin (9). Based on 1D- and 2D-NMR data (COSY, HMQC, HMBC), the structures of the new compounds were deduced to be (E)-1-[(3-methylbut-2-enyl)oxy]-2-methoxy-4-(prop-1-enyl)benzene (1) and 11-O-debenzoyl-11alpha-O-2-methylcyclopent-1-enecarboxyltashironin (8). Compounds 1-9 were screened for anti-HIV activity in vitro whereby compounds 5 and 7 possessed moderate anti-HIV activity with EC50 values of 16.0 and 5.1 microM with SI values of 18.2 and 15.6, respectively.     

Inhibitory constituents of lipopolysaccharide-induced nitric oxide production in BV2 microglia isolated from Amomum tsao-ko

A methanolic extract of the fruits of AMOMUM TSAO-KO (Zingiberaceae) significantly attenuated nitric oxide production in lipopolysaccharide-simulated BV2 microglia. Two new bicyclic nonanes characterized as 6,7-dihydroxy-indan-4-carbaldehyde ( 1) and 6-hydroxy-indan-4-carbaldehyde ( 2) were isolated with the eleven known compounds 6,7-dihydroxy-3,7-dimethyloct-2-enoic acid ( 3), tsaokoin ( 4), isotsaokoin ( 5), 8-oxogeraniol ( 6), P-menth-1-ene-5,6-diol ( 7), 3alpha-hydroxycarvotagenone ( 8), tsaokoarylone ( 9), 1,7-bis(4-hydroxy-3-methoxyphenyl)-4,6-heptadien-3one ( 10), (+)-hannokinol ( 11), MESO-hannokinol ( 12) and hannokinin ( 13), from the fruits of A. TSAO-KO using bioactivity-guided fractionation. All thirteen compounds significantly inhibited lipopolysaccharide-induced nitric oxide production in BV2 microglial cells at concentrations ranging from 1 microM to 100 microM.     

Synthesis and analgesic, anti-inflammatory activities of 3-(3-methoxyphenyl)-2-substituted amino-quinazolin-4(3H)-ones

A variety of novel 3-(3-methoxyphenyl)-2-substituted amino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(3-methoxyphenyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(3-methoxyphenyl)-quinazolin-4(3H)-one was synthesized from 3-methoxy aniline. The title compounds were investigated for analgesic, anti-inflammatory, and ulcerogenic behavior. Among these the compound 2-(1-methyl butylidene-hydrazino)-3-(3-methoxyphenyl)-3H-quinazolin-4-one (AS3) emerged as the most active compound for the analgesic activity, while the compound 2-(1-ethyl propylidene-hydrazino)-3-(3-methyoxyphenyl)-3H-quinazolin-4-one (AS2) showed most potent anti-inflammatory activity of the series and these compounds are moderately more potent when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.     

Antioxidative 7-oxodehydropodocarpane-type trinorditerpenes from the bark of Taiwania cryptomerioides

Five new 7-oxopodocarpane-type trinorditerpenes together with 1beta,13,14-trihydroxy-8,11,13-podocarpatrien-7-one ( 1) were isolated from the bark of Taiwania cryptomerioides. By using NMR and other spectral methods, the structures of five new compounds, 14-hydroxy-13-methoxy-8,11,13-podocarpatriene-3,7-dione ( 2), 1beta,14-dihydroxy-13-methoxy-8,11,13-podocarpatrien-7-one ( 3), 13,14-dihydroxy-8,11,13-podocarpatriene-3,7-dione ( 4), 3beta,13,14-trihydroxy-8,11,13-podocarpatrien-7-one ( 5), and 1beta,13,14-trihydroxy-8,11,13-podocarpatriene-2,7-dione ( 6), were elucidated. Compounds 1, 4, 5, and 6 exhibited strong antioxidative activity.