Armenin and isoarmenin--two prenylated coumarins from the aerial parts of Artemisia armeniaca

The reversed-phase (RP) preparative HPLC analyses of the MeOH extract of the aerial parts of Artemisia armeniaca yielded four prenylated coumarins, 7-hydroxy-8-(4-hydroxy-3-methylbutoxy)coumarin (named armenin), 8-hydroxy-7-(4-hydroxy-3-methylbutoxy)coumarin (named isoarmenin), lacarol, and deoxylacarol, together with five other compounds, including three flavonoid glycosides, quercetin 3-O-β-D-glucopyranoside, rutin, and kaempferol 3-O-β-D-glucopyranoside, and chlorogenic acid, and tryptophan. (10E,12Z)-9-Hydroxyoctadeca-10,12-dienoic acid (β-dimorphecolic acid) was isolated from the CH(2)Cl(2) extract. Armenin and isoarmenin were new coumarins. Structures of all compounds were determined by spectroscopic means, including UV, MS, 1D- and 2D-NMR. The in vitro free-radical-scavenging property of the extracts and isolated compounds was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.     

Spasmolytic flavonoids from Syzygium samarangense (Blume) Merr. & L.M. Perry

The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10-1000 microg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethyl-flavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 +/- 69.4, 77.2 +/- 43.5, 142.4 +/- 58.6 and 178.5 +/- 37.5 microg/ml (mean +/- SEM), respectively. The dihydrochalcone derivative of compound 1, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0.16 +/- 0.04 microg/ml. This is the first report of the relaxant activity of chalcones, specifically of compounds 1-3.     

Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains

An experimental and theoretical study was performed on the anti-staphylococcal activity of 18 natural and synthetic flavonoids against methicillin-resistant Staphylococcus aureus strains. The analysed flavonoids belong to three well-differentiated structural patterns: chalcones, flavanones and flavones. The quantitative analysis of the anti-staphylococcal activity of the compounds was carried out by determining their percent inhibition degree. The hierarchical cluster analysis method was used to analyse the anti-MRSA activity of the compounds. With this methodology, the flavonoids were classified into four groups according to their anti-staphylococcal activity (high, sufficient, intermediate and low). The carbonylic region is of importance because it is part of the bioactive region inducing anti-MRSA activity in the flavonoid molecules. The introduction of OH groups in positions 2' of chalcones and 5 of flavanones (or flavones) increases flavonoid activity, while the OCH(3)groups produce the reverse effect. Using the experimental anti-MRSA activity data of flavonoids and six quantum chemical parameters calculated by means of the AM1 semiempirical molecular orbital method, a very good quantitative structure-activity relationship was obtained (confidence range: 95%; significance level for tests: 0.05; correlation coefficient=0.9842). The selected parameters explain 96.86% of the percent inhibition degree. The obtained relation is consistent with the conclusions formulated in this paper and serves as a theoretical support for some of them. Finally, it is concluded that the flavonoids chalcone, 2'(OH)-chalcone, 2',4'(OH)(2)-chalcone and 2',4(OH)(2)-chalcone might constitute promising therapeutic agents against infections with methicillin-resistant S. aureus strains.     

旱前胡的化学成分

从云南产早前胡(Ligusticum daucoides Franch.)(伞形科)根的脂溶性部分分离了11个化合物,分别为香豆素化合物:columbianadin,isoedultin,archangelicin,旱前胡甲素(daucoidin A),旱前胡乙素(dsucoidin B),佛手柑内酯(bergapten),非香豆素化合物:falcarindiol(7),阿魏酸(ferulic acid),蜡酸(cerotic acid),β-谷甾醇(β-sitosterol),胡萝卜甙(daucosterol)。其中,化合物4和5是新的香豆素化合物,经化学方法及光谱测定,证明其结构为:4是3′去乙酰基isoedultin,即:2′(S)-(1″,1″-二甲基,1″-当归酰氧基)-3′(R)-羟基-角型二氢呋喃香豆素[2′(S)-(1″,1″-dimethvl,1″-angelovloxv)—3′(R)-hydroxy angular dihydrofuranocoumarin];5是2′-(1″-甲基,1″-羟基,1″-当归酰氧亚甲基)-角型二氢呋喃香豆素[2′-(1″-methyl,1″-hydroXy,1″-angeloyloxy-methylene)angular dihydrofuranocoumarin]。     

Chemosystematic value of chemical constituents from Scabiosa hymettia (Dipsacaceae)

The first phytochemical investigation of Scabiosa hymettia led to the isolation and characterization of nine known compounds, 2-10, and of the new kaempferol derivative 1. In total, two flavonoids, three coumarins, three iridoids, and two phenolic constituents were obtained. The chemosystematic value of these compounds, as well as the metabolic relationship between swertiamarin (6) and the other isolated coumarins, are discussed. Both the extracts as well as all isolated constituents of S. hymettia were evaluated for their antimicrobial activities against six Gram-positive or Gram-negative bacteria, and against three human pathogenic fungi. The new compound 1 was found to exhibit the highest activity against all organisms tested.     

Flavonoids from seeds of Camellia semiserrata Chi. and their estrogenic activity

Two new flavonol glycosides and three known flavonoids were isolated from seeds of Camellia semiserrata Chi. The structures of these new flavonol glycosides were established as kaempferol 3-O-[(2',3',4'-triacetyl)-alpha-L-rhamnopyranosyl(1-->3)(2',4'-diacetyl)-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside] and kaempferol 3-O-[(3',4'-diacetyl)-alpha-L-rhamnopyranosyl(1-->3)(2',4'-diacetyl)-alpha-L-rhamnopyranosyl(1-->6)-beta-D-glucopyranoside] by spectroscopic methods. The estrogenic activity of these compounds was investigated by a recombinant yeast screening assay.     

Natural products isolated from Mexican medicinal plants: Novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1

Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis are used in Latin American folk medicine. Four natural xanthones, an acetylated derivative, and two coumarins were obtained from C. brasiliense. Two flavanones were extracted from L. oaxacensis and one chalcone from L. guatemalensis. These compounds were tested as substrates and inhibitors for two recombinant sulfotransferases (SULTs) involved in the metabolism of many endogenous compounds and foreign chemicals. Assays were performed using recombinant phenol-sulfotransferase (SULT1A1) and hydroxysteroidsulfotransferase (SULT2A1). Three of the five xanthones, one of the flavonoids and the coumarins tested were substrates for SULT1A1. None of the xanthones or the flavonoids were sulfonated by SULT2A1, whereas the coumarin mammea A/BA was a substrate for this enzyme. The natural xanthones reversibly inhibited SULT1A1 with IC₅₀ values ranging from 1.6 to 7 μM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC₅₀ values of 26-204 μM). The flavonoids inhibited SULT1A1 with IC₅₀ values ranging from 9.5 to 101 μM, which compared with amounts needed to inhibit SULT2A1 (IC₅₀ values of 11 to 101 μM). Both coumarins inhibited SULT1A1 with IC₅₀ values of 47 and 185 μM, and SULT2A1 with IC₅₀ values of 16 and 31 μM. The acetylated xanthone did not inhibit either SULT1A1 or SULT2A1 activity. Rotenone from a commercial source had potency comparable to that of the flavonoids isolated from Lonchocarpus for inhibiting both SULTs. The potency of this inhibition depends on the position and number of hydroxyls. The results indicate that SULT1A1, but not SULT2A1, is highly sensitive to inhibition by xanthones. Conversely, SULT2A1 is 3-6 times more sensitive to coumarins than SULT1A1. The flavonoids are non-specific inhibitors of the two SULTs.

Collectively, the results suggest that these types of natural products have the potential for important pharmacological and toxicological interactions at the level of phase-II metabolism via sulfotransferases.     

Rare biscoumarins and a chlorogenic acid derivative from Erycibe obtusifolia

Three coumarins, 7,7'-dihydroxy-6,6'-dimethoxy-3,3'-biscoumarin (1), 7,7'-dihydroxy-6,6'-dimethoxy-8,8'-biscoumarin (2) and 7-O-[4'-O-(3',4'-dihydroxycinnamyl)-beta-d-glucopyranosyl]-6-methoxycoumarin (3), and a chlorogenic acid derivative, methyl-3-O-(4'-hydroxy-3',5'-dimethoxybenzoyl)-chlorogenate (4) were isolated from the roots of Erycibe obtusifolia along with four known coumarins, scopoletin (5), scopolin (6), cleomiscosin A (7) and cleomiscosin B (8). Their structures were elucidated by spectroscopic methods. Among them, compounds (1) and (2) are rare carbon-carbon linked symmetrical biscoumarins.     

Coumarin glucosides from Cruciata taurica

Two new coumarin glycosides (1 and 2) along with two known coumarin glucosides, daphnin (3) and daphnetin glucoside (4) were isolated from the aerial parts of Cruciata taurica. The structures of the new compounds were elucidated by spectral methods and chemical means as 7-O-(6' -acetoxy-beta-D-glucopyranosyl)-8-hydroxycoumarin (1) and 7-O-[6 '-O-(3',4'-dihydroxycinnamoyl)-beta-D-glucopyranosyl]-8-hydroxycoumarin (2). The phylogenetic significance of coumarins in C. taurica was discussed.     

Aldose-reductase- and protein-glycation-inhibitory principles from the whole plant of Duchesnea chrysantha

Ellagic acid (1), 3,3'-di-O-methylellagic acid (2), 3,3',4-tri-O-methylellagic acid (3), isovitexin (4), kaempferol 3-O-beta-D-glucuronide methyl ester (5), quercetin 3-O-alpha-L-arabinopyranosyl-(1-->6)-beta-D-galactopyranoside (6), ursolic acid, pomolic acid, tormentic acid, euscaphic acid, euscaphic acid 28-O-beta-D-glucopyranoside, and maslinic acid were isolated from the AcOEt- and BuOH-soluble MeOH extract of Duchesnea chrysantha (whole plant). The isolates were subjected to in vitro bioassays to evaluate their inhibitory activity on rat-lens aldose reductase (RLAR) and formation of advanced glycation end products (AGEs). The ellagic acids and flavonoids, compounds 1-6, exhibited moderate inhibitory effects on RLAR. However, compounds 1 and 4-6 showed excellent inhibitory activities towards the formation of AGEs. This is the first report that 4 and 6 exhibit inhibitory activity towards AR and AGEs formation.     

Antimicrobial and radical scavenging flavonoids from the stem wood of Erythrina latissima

From the stem wood of Erythrina latissima, two isoflavones and a flavanone were isolated and characterized as 7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)isoflavone (erylatissin A), 7,3'-dihydroxy-6',6'-dimethyl-4',5'-dehydropyrano [2',3': 4',5']isoflavone (erylatissin B), (-)-7,3'-dihydroxy-4'-methoxy-5'-(gamma,gamma-dimethylallyl)flavanone (erylatissin C), respectively, in addition to 10 known flavonoids. Structures of these compounds were determined on the basis of their spectroscopic data. These compounds showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Candida mycoderma. The isolated compounds also exhibited weak radical scavenging properties towards DPPH radical.     

(Rel)-1beta,2alpha-di-(2,4-dihydroxy-6-methoxybenzoyl)-3beta, 4alpha-di-(4-methoxyphenyl)-cyclobutane and other flavonoids from the aerial parts of Goniothalamus gardneri and Goniothalamus thwaitesii

The aerial parts of Goniothalamus gardneri (Annonaceae) has yielded the known flavonoids 2'-hydroxy-4,4',6'-trimethoxychalcone (flavokawain A), 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone, 4,2',4'-trihydroxy-6'-methoxydihydrochalcone, 5,7,4'-trimethoxyflavanone (naringenin trimethyl ether) and 7-hydroxy-5,4'-dimethoxyflavanone (tsugafolin) together with three novel compounds, the dimer characterised as (rel)-1beta,2alpha-di-(2,4-dihydroxy-6-methoxybenzoyl)-3beta,4alpha-di-(4-methoxyphenyl)-cyclobutane, 2',4'-dihydroxy-4,6'-dimethoxychalcone and 2'-hydroxy-4,4',6'-trimethoxydihydrochalcone. The last two have previously been synthesised but appear to be new natural products. A similar study of the aerial parts of G. thwaitesii led only to the isolation of the known flavonoids myricetin 4'-O-methyl ether-3-O-alpha-L-rhamnopyranoside (mearnsitrin) and myricetin-3-O-methyl ether (annulatin), together with the triterpenes friedelinol, friedelin and betulinic acid. All compounds were identified by spectroscopic analysis and, for known compounds, by comparison with published data.     

Flavonoids from Limnophila indica

Two flavonoids, (2S)-5,7,3',4'-tetramethoxyflavanone (1) and 5,7,2',5'-tetramethoxyflavone (2) together with three known flavonoids, 7-O-methylwogonin (3), skullcapflavone I (4) and 5-hydroxy-7,2'-dimethoxyflavone (5) were isolated from the whole plant of Limnophila indica. The structures of compounds 1-5 were elucidated on the basis of spectral and chemical studies.     

四合木的化学成分研究

从我国蒺藜科特有属植物四合木（Taraena mongolica Maxim）的全株中首次得到了五种化合物。应用光谱等检测方法,对其结构进行了鉴定。分别鉴定为：十四碳酸月桂醇酯（1）、羽扇豆醇（2）、β-谷甾醇（3）、5,7,3＇,4＇-四羟基-3-甲氧基黄酮（4）、5,7,4’-三羟基-3,3’-二甲氧基黄酮（5）。上述成分均为首次从四合木中得到。其中5,7,3’,4＇-四羟基-3-甲氧基黄酮表现出较高的抗氧化活性。     

Modulation of MRP1 protein transport by plant, and synthetically modified flavonoids

The influence of novel synthetic and plant origin flavonoids on activity of multidrug resistance-associated protein (MRP1) was investigated in human erythrocytes used as a cell model expressing MRP1 in plasma membrane. The fluorescent probe, BCPCF (2', 7'-bis-(3-carboxy-propyl)-5-(and-6)-carboxyfluorescein), was applied as a substrate for MRP1 multidrug resistance transporter. The effect of compounds belonging to different classes of natural flavonoids: flavone, flavonol, isoflavones and flavanolignan was compared with action of new synthetic derivatives of genistein. Most of the flavonoids showed strong or moderate ability to inhibit transport carried out by MRP1. Inhibitory properties of flavonoids were compared to the effects of indomethacin, probenecid and MK-571 known as MRP1 inhibitors. Studying the influence of new synthetic genistein derivatives on BCPCF transport we have found that the presence of hydrophobic groups substituting hydrogen of hydroxyl group at the position 4' in ring B of isoflavone is more important for inhibitory properties than hydrophobic substitution at the position 7 in ring A. In case of naturally occurring isoflavones the replacement of hydrogen at position 4' by hydrophobic ring structure seems also to be favourable for inhibition potency.     

Antioxidative activity of natural products from plants

A variety of flavonoids, lignans, an alkaloid, a bisbenzyl, coumarins and terpenes isolated from Chinese herbs was tested for antioxidant activity as reflected in the ability to inhibit lipid peroxidation in rat brain and kidney homogenates and rat erythrocyte hemolysis. The pro-oxidant activities of the aforementioned compounds were assessed by their effects on bleomycin-induced DNA damage. The flavonoids baicalin and luteolin-7-glucuronide-6'-methyl ester, the lignan 4'-demethyldeoxypodophyllotoxin, the alkaloid tetrahydropalmatine, the bisbenzyl erianin and the coumarin xanthotoxol exhibited potent antioxidative activity in both lipid peroxidation and hemolysis assays. The flavonoid rutin and the terpene tanshinone I manifested potent antioxidative activity in the lipid peroxidation assay but no inhibitory activity in the hemolysis assay. The lignan deoxypodophyllotoxin, the flavonoid naringin and the coumarins columbianetin, bergapten and angelicin slightly inhibited lipid peroxidation in brain and kidney homogenates. It is worth stressing that the compounds with antioxidant effects in this assay, with the exception of tetrahydropalmatin and tanshinone I, have at least one free aromatic hydroxyl group in structure. Obviously, the aromatic hydroxyl group is very important for antioxidative effects of the compounds. None of the compounds tested exerted an obvious pro-oxidant effect.     

Anti-inflammatory and antinociceptive activity of flavonoids isolated from Viscum album ssp. album

Viscum album L. has been used in the indigenous systems of medicine for treatment of headache and some inflammatory diseases. In order to evaluate this information, antinociceptive and anti-inflammatory activities of the five flavonoids (5,7-dimethoxy naringenin or 4',6'-dimethoxy chalcononaringenin) derivatives, isolated from the ethyl acetate fraction of the extract from V. album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4'-O-beta-D-glucopyranoside (1), 2'-hydroxy-4',6'-dimethoxy-chalcone-4-O-beta-D-glucopyranoside (2), 5,7-dimethoxy-flavanone-4'-O-[2"-O-(5"'-O-trans-cinnamoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (3), 2'-hydroxy-4',6'-dimethoxy-chalcone-4-O-[2"-O-(5"'-O-trans-cinnamoyl)-beta-Dapiofuranosyl]-beta-D-glucopyranoside (4), 5,7-dimethoxy-flavanone-4'-O-[beta-D-apiofuranosyl-(1 --> 2)]-beta-D-glucopyranoside (5). For the antinociceptive activity assessment the p-benzoquinone-induced writhing test and for the anti-inflammatory activity the carrageenan-induced hind paw edema model in mice were used. The ethyl acetate fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose were shown to possess remarkable antinociceptive and anti-inflammatory activities per os without inducing any apparent acute toxicity as well as gastric damage.     

Coumarins from Malaysian Micromelum minutum

In a continuation of our study of the Rutaceae, detailed chemical investigation on Micromelum minutum (Rutaceae) collected from Sepilok, Sabah, Malaysia gave four new coumarins. The structures of the coumarins have been fully characterised by spectroscopic methods as 3",4"-dihydrocapnolactone 1, 2',3'-epoxyisocapnolactone 2, 8-hydroxyisocapnolactone-2',3'-diol 3 and 8-hydroxy-3",4"-dihydrocapnolactone-2',3'-diol 4.     

Flavonoids from the leaves and stems of Dodonaea polyandra: a Northern Kaanju medicinal plant

Three prenylated flavonoids 5,7,4'-trihydroxy-3'(3-methylbut-2-enyl)-3-methoxy flavone, 5,7-dihydroxy-3'(3-methylbut-2-enyl)-3,4'-dimethoxy flavone and 5,7,4'-trihydroxy-3',5'(3-methylbuyt-2-enyl)-3-methoxy flavone together with three other known flavonoids were isolated from the medicinal plant Dodonaea polyandra. The plant is used in the traditional medicine system of Northern Kaanju people of Cape York Peninsula, Queensland, Australia. The extracts studied have previously been found to possess anti-inflammatory activity. Successive fractionation of leaf and stem extracts by column and high performance liquid chromatography led to the isolation of these compounds. Their structures were determined using a number of spectroscopic techniques including 1D and 2D NMR and high resolution mass spectroscopy. The structural elucidation is reported herein accompanied by full 1H and 13C NMR spectroscopic data. Spectroscopic data of known compounds was in agreement with that previously reported in literature.     

Flavonoids from Andrographis lineata

Three flavonoids, 5,7,2',3',4'-pentamethoxyflavone (1), 2'-hydroxy-2,4',6'-tri methoxychalcone (2) and dihydroskullcapflavone I (3), together with 17,19,20-trihydroxy-5beta, 8alpha H, 9beta H,10alpha-labd-13-en-16,15-olactone (4), a known diterpenoid and six known flavonoids, 5-hydroxy-7,8-dimethoxyflavanone (5), 5-hydroxy-7,8,2',3',4'-pentamethoxyflavone (6), 5,2'-dihydroxy-7-methoxyflavanone (7), 5,2'-dihydroxy-7,8-dimethoxyflavone (8), 5,2'-dihydroxy-7-methoxyflavone (9) and 5,2'-dihydroxy-7-methoxyflavone 2'-O-beta-D-glucopyranoside (10) were isolated from the whole plant of Andrographis lineata. The structures of these compounds were elucidated on the basis of spectral and chemical studies.