Antiproliferative constituents in plants 10. Flavones from the leaves of Lantana montevidensis Briq. and consideration of structure-activity relationship

The flavonoid fraction from the leaves of Lantana montevidensis Briq. (Verbenaceae) showed antiproliferative activity against human gastric adenocarcinoma (MK-1, GI50: 12 microg/ml), human uterus carcinoma (HeLa, 5 microg/ml), and murine melanoma (B16F10, 5 microg/ml) cells in vitro. Bioactivity-guided chemical investigation of the fraction has resulted in the isolation of apigenin (10) and ten 5,6,7-oxygenated flavones: cirsilineol (1), eupatorin (2), 5,4'-dihydroxy-6,7,3',5'-tetramethoxyflavone (3), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (4), 5,6,4'-trihydroxy-7,3',5'-trimethoxyflavone (5), 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (6), 5,3',4'-trihydroxy-6,7,5'-trimethoxyflavone (7), cirsiliol (8), hispidulin (9), and eupafolin (11). Antiproliferative activity of the isolated flavones, some other related flavones (luteolin, baicalein, 6-hydroxyluteolin, pectolinarigenin, jaceosidin, desmethoxycentaureidin, eupatilin, and chrysin) from other plant materials, and synthetic 6- and 7-methoxyflavones was evaluated, and the structure-activity relationships were examined.     

中间锦鸡儿黄酮类成分的研究

目的研究中间锦鸡儿的化学成分。方法用溶剂法、色谱法分离化学成分，用波谱法鉴定其结构。结果从中间锦鸡儿中分离得到10个黄酮类化合物，分别鉴定为5,7,4′-三羟基-3,3′-二甲氧基黄酮(1)，3,5,7,8,4′-五羟基-3′-甲氧基黄酮(2),槲皮素(3),柠檬黄酮醇(4),槲皮素-3-甲醚(5)，2(S)-7,3′,5′-三羟基二氢黄酮(6)，5,7,3′,4′-四羟基-3,8-二甲氧基黄酮(7),紫铆查尔酮（8）,甘草素（9）和5,7,4′-三羟基-3,8二甲氧基黄酮（10）。结论化合物6为新化合物，其余皆首次从中间锦鸡儿中分离得到。     

穿心莲根的化学成分研究

为研究常用中药爵床科植物穿心莲(Andrographis paniculata)根的化学成分,运用各种色谱方法从安徽临泉产穿心莲根的80%乙醇提取物中分离并鉴定了28个化合物,其中20个黄酮:5,5'-二羟基-7,8,2'-三甲氧基黄酮(1)、5-羟基-7,8,2',6'-四甲氧基黄酮(2)、5,3'-dihydroxy-7,8,4',-trimethoxyflavone(3)、2'-羟基-5,7,8-三甲氧基黄酮(4)、5-羟基-7,8,2',3',4'-五甲氧基黄酮(6)、wightin(7)、5,2',6'-trihydroxy-7-methoxyflavone 2'-O-β-D-glucopyranoside(8)、5,7,8,2'-四甲氧基黄酮(10)、5-羟基-7,8-二甲氧基二氢黄酮(11)、5-羟基-7,8-二甲氧基黄酮(12)、5,2'-二羟基-7,8-二甲氧基黄酮(13)、5-羟基-7,8,2',5'-四甲氧基黄酮(14)、5-羟基-7,8,2',3'-四甲氧基黄酮(15)、5-羟基-7,8,2'-三甲氧基黄酮(16)、5,4'-二羟基-7,8,2',3'-四甲氧基黄酮(17)、二氢黄芩新...     

Highly Methylated 6-Hydroxyflavones and Other Flavonoids from Thymus piperella

From the aerial parts of THYMUS PIPERELLA, the free flavone aglycones 5,6-dihydroxy-7,8,4'-trimethoxyflavone ( 1), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone ( 2), 5,6-dihydroxy-7,3',4'-trimethoxyflavone ( 3), ladanein ( 4) (5,6-dihydroxy-7,4'-dimethoxy-flavone), 5-hydroxy-7,4'-dimethoxyflavone ( 5) and apigenin ( 6), the flavanones naringenin ( 7) and eriodictyol ( 8), and the flavone glycosides vicenin-2 ( 9), apigenin-7- O-beta- D-glucoside (10) and luteolin-7- O-beta- D-glucoside ( 11), have been isolated and identified. This is the first time that 5,6-dihydroxy-7,8,4'-trimethoxyflavone has been found as a natural product.     

Flavonoids from Artemisia gmelinii Web. ex Stechm.

Phytochemical investigation of Artemisia gmelinii Web. ex Stechm. led to the isolation of 11 known flavonoids. Their structures were identified as genkwanin (1), hispidulin (2), 3'-hydroxy-genkwanin (3), chrysoeriol (4), apigenin (5), 5,7,3',4'-tetrahydroxy-6,5'-dimethoxy-flavone (6), kumatakenin (7), quercetin (8), patuletin (9), quercetagetin-3,6,7-trimethylether (10) and 7,3',4'-trihydroxy-3-methoxy-flavone (11) by spectroscopic methods. Ten compounds (2-11)were isolated from this title plant for the first time, and five compounds (3, 6, 7, 10 and 11) were isolated from genus Artemisia for the first time.     

鸡血藤的化学成分研究

目的研究中药鸡血藤(Spatholobus suberectus Dunn)的化学成分。方法利用多种柱色谱方法进行分离纯化,根据光谱数据和化学方法进行结构鉴定。结果从鸡血藤70%乙醇浸膏的乙酸乙酯部分分离鉴定了8个化合物,分别是:密花豆素(1)、芒柄花素(2)、大豆苷元(3)、毛蕊异黄酮(4)、焦性粘液酸(5)、间苯三酚(6)、琥珀酸(7)、β-谷甾醇(8)。结论化合物1为7,3′,4′-三羟基-6-甲氧基二氢黄酮,是1个新化合物,命名为密花豆素,化合物4,5,6和7为首次从本属植物中得到。     

Antioxidant activity of isoflavones and biflavones isolated from Godoya antioquiensis

Two biflavones, ochnaflavone (1) and 2",3"-dihydroochnaflavone (2), and two isoflavones, 5,7,4'-trihydroxy-3',5'-dimethoxyisoflavone (piscigenin) (3) and 5,4'-dihydroxy-7,3',5'-trimethoxyisoflavone (4), a new natural compound, were isolated from the leaves of Godoya antioquiensis (Ochnaceae). Their structures were determined on the basis of spectral data and by comparison with data reported in the literature. The isolated compounds were evaluated for their radical scavenging activity using the NBT (nitrobluetetrazolium)/hypoxanthine superoxide and the .OH/luminol chemiluminescence methods. The isolated isoflavones were found to exhibit a strong hydroxyl radical scavenging activity and a moderate inhibition of the superoxide anion, whereas the two biflavones were inactive in the superoxide anion assay and showed a low hydroxyl radical scavenging activity.     

Chemical constituents, antimicrobial and antimalarial activities of Zanthoxylum monophyllum

From the leaves and bark of Zanthoxylum monophyllum, a new lignan, 3-methoxy-3',4'-methylenedioxylignan-4,8,9,9'-tetraol (1), has been isolated along with 22 known compounds (2- 23), fifteen of them reported for the first time from Z. monophyllum. Their chemical structures were elucidated using detailed spectroscopic studies and chemical analysis. All compounds were evaluated for antimicrobial and antiprotozoal activities. Alkaloids BIS-[6-(5,6-dihydro-chelerythrinyl)] ether (2) and 6-ethoxy-chelerythrine (4) exhibited strong activity against Aspergillus fumigatus and methicillin-resistant Staphylococcus aureus (MRSA). Compound 4-methoxy-N-methyl-2-quinolone (9) exhibited significant activity against MRSA (IC50 value of 8.0?μM) while compound 5,8,4'-trihydroxy-3,7,3'-trimethoxyflavone (10) showed weak activity against Plasmodium falciparum.     

Flavonoids from the leaves of Pleioblastus argenteastriatus

A new flavonoid, 5,7,3'-trihydroxy-6-C-beta-D-digitoxopyranosyl-4'-O-beta-D-glucopyranosyl flavonoside (1), along with four known flavonoids 5,7,4'-trihydroxy-3',5'-dimethoxy flavone (2), 5,3',4'-trihydroxy-7-O-beta-D-glucopyranosyl flavonoside (3), 5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D-glucopyranosyl flavonoside (4), 5,3',4'-trihydroxy-6-C-[beta-D-glucopyranosyl-(1 --> 6)]-beta-D-glucopyranosyl flavonoside (5) were isolated from 95% EtOH extract of the leaves of Pleioblastus argenteastriatus. Their structures were determined on the basis of spectroscopic techniques and chemical methods.     

Flavans from the leaf of Ilex centrochinensis

Phytochemical investigation of the leaf of Ilex centrochinensis led to the isolation and characterization of four flavans, one flavanone (5), and one flavone (6), including a new compound whose structure was elucidated as (2S)-5,3',4'-trihydroxy-7-methoxyflavan (1) and a new natural product whose structure was elucidated as (2S)-5-hydroxy-7,3',4'-trimethoxyflavan (4) on the basis of spectroscopic methods especially 1D and 2D NMR, CD, and mass spectral analyses. Compounds 1 and 4 exhibited weak cytotoxic activity against Huh7 cell line and no cytotoxic activity against Caco-2 cell line.     

Phenolic compounds with anti-inflammatory activity from Eupatorium buniifolium.

Anti-inflammatory activity was detected in the CH(2)Cl(2) extract of the aerial parts of Eupatorium buniifolium using the TPA-mouse ear model. Three compounds isolated from this extract, by bioassay-guided fractionation, significantly inhibited the inflammatory response. The compounds were identified as 5,7,5'-trihydroxy-3,6,2',4'-tetramethoxyflavone (1), scopoletin (2) and centaureidin (3) which inhibited the edema by 67.3 %, 59.8 % and 49.7 %, respectively, at a dose of 1 mg/ear.     

Three new C-flavonoids from Corallodiscus flabellata

Three new C-glycosylflavones, named 5,7,4'-trihydroxy-6-methoxy-8-C-[beta-D-xylopyranosyl- (1 --> 2)]-beta-D-glucopyranosyl flavonoside (1), 5,7,4'-trihydroxy-8-methoxy-6-C-[beta-D-xylopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl flavonoside (2), and 5,3',4'-trihydroxy-7,8-dimethoxy-6-C-[beta-D-xylopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl flavonoside (3), along with two known compounds 5,4'-dihydroxy-7-methoxy-6-C-glucopyranosyl-flavonoside (4), 3-methoxy-4-hydroxymethyl benzoate (5) were isolated from 70% acetone extract of Corallodiscus flabellata. Their structures were identified on the basis of spectroscopic techniques and chemical methods.     

Inhibition of aldose reductases from rat and bovine lenses by flavonoids

Thirty flavones, four isoflavones and thirteen coumarins were tested as inhibitors of lens aldose reductase, which is believed to participate in the initiation of cataract formation in diabetes. Many were found to be potent inhibitors, and the two most potent ones were axillarin (5,7,3',4'-tetrahydroxy-3,6-dimethoxyflavone) and 6,3',4'-trihydroxy-5,7,8-trimethoxyflavone (LARI 1). These two flavones inhibited aldose reductase purified from rat lens with IC50 values of 2.6 X 10(8) and 3.6 X 10(8) M respectively. They also inhibited aldose reductase purified from bovine lens with IC50 values of 1.8 X 10(7) M. The potencies of the two compounds were superior to those of all the previously reported inhibitors of aldose reductase. Inhibition of rat and bovine lens aldose reductases by the two compounds was of a non-competitive type with DL-glyceraldehyde as the variable substrate. Some flavones including axillarin and LARI 1 were found to be poorly or scarcely inhibitory against several adeninenucleotide-requiring enzymes, which are involved in glycolysis and other metabolic reactions. These results obtained show that the two flavones have some features which may be required in clinically useful drugs for diabetic patients. All the potent inhibitors of the compounds tested had a flavone skeleton, one (or two free) hydroxyl(s) in ring C, and more than three hydroxyls (free or methylated) in ring A. The possible relationships of structures to inhibitory potencies of the compounds tested are discussed.     

Methylated Flavones from Teucrium polium

The following four methylated flavones were obtained from the leaves of TEUCRIUM POLIUM L. (Labiatae). 4', 5-dihydroxy-6,7-dimethoxyflavone (cirsimaritin); 3', 5 dihydroxy-4',6,7-trimethoxyflavone (eupatorin); 5-hydroxy-4',7-dimethoxyflavone (apigenin-4', 7-dimethylether); 4', 5, 3'-trihydroxy-6,7-dimethoxyflavone (cirsiliol). One of these (4', 5-dihydroxy- 6,7-dimethoxyflavone) has been already reported in the same plant by Brieskorn and Biechele (1).     

Inhibitory effect of flavonoids on N-acetylation of 5-aminosalicylic acid in cultured rat hepatocytes

5-Aminosalicylic acid (5-ASA) is an effective drug for the treatment of ulcerative colitis and Crohn's disease. A large group of flavonoids was investigated for their inhibitory effects on the N-acetyl-conjugation of 5-ASA in rat hepatocytes and subcellular preparations. When added to cultured hepatocytes, some flavonoids inhibited the production of N-acetyl-5-aminosalicylic acid (5-AcASA) with potencies that depended on the specific structure of flavonoids. Among the flavonols, quercetin, kaempferol and galangin had inhibitory activity with a tendency to be more effective at increasing the number of hydroxyl substitutions in the B-ring. Flavones such as luteolin, apigenin and chrysin were as effective as the corresponding three flavonols above. 7,3',4'-OH flavone was more effective than other simple flavones such as 7-, 5-, 3-, 7,3-, 7,4'- and 3',4'-OH flavones. Isoflavones were relatively weak inhibitors. Taxifolin and catechins had little or no inhibitory effect. These data suggest that the presence of C7 hydroxyl substitution on the A-ring and the catechol group on the B-ring in the flavone structure is required for effective inhibitory activity. The inhibitory effect of flavonoids on N-acetyl-conjugation of 5-ASA was also examined by incubating 5-ASA with isolated liver cytosolic preparations. The active flavonoids in the cells inhibited the N-acetylation of 5-ASA in the cell-free enzymatic preparations with a potency comparable to that for cultured rat hepatocytes.     

Antifungal chalcones from Maclura tinctoria

Five prenylated flavonoids, including one new natural product, were isolated from an ethanol extract of the leaves of Maclura tinctoria (L.) Gaud. The new compound has been characterized as 2',4',4,2'-tetrahydroxy-3'-[3'-methylbut-3'-enyl]chalcone (1). The known compounds were identified as 2',4',4-trihydroxy-3'-[3'-methylbut-3'-enyl]chalcone (isobavachalcone) (2), 4,2'-dihydroxy-2'-[1-hydroxy-1-methylethyl]-2',3'-dihydrofurano[4',5':3',4']chalcone (bakuchalcone) (3), 4,4',5'-trihydroxy-6',6'-dimethyldihydropyrano[2',3':5',6']chalcone (bavachromanol) (4), and 5,7,3',4'-tetrahydroxy-6,8-diprenylisoflavone (6,8-diprenylorobol) (5). All the isolated compounds were evaluated against the AIDS-related opportunistic fungal pathogens, Candida albicans and Cryptococcus neoformans. Compound 2 was active against both yeasts.     

5, 6, 4'-Trihydroxy-7, 3'-dimethoxyflavone and other Methoxylated Flavonoids Isolated from Thymus satureiodes

From the aerial parts of THYMUS SATUREIOIDES, two flavonoids, new for this species, have been identified: 5-hydroxy-6,7,3',4'-tetramethoxyflavone and 5,6,4'-trihydroxy-7,3'-dimethoxyflavone. This last compound has previously been isolated once from other species of Labiatae.     

Isolation and structure elucidation of viscoazucine, a novel sesquiterpene from Polygonum viscosum

A new sesquiterpene, 1,4-dimethoxycarbonyl-7-(1-methylethyl)- 3,3a,6,7,8,8a-hexahydroazulene (viscoazucine) (1), and a known flavone, 3',5,7-trihydoxy-3,4',5'-trimethoxyflavone (4), have been isolated from Polygonum viscosum. The structures of these compounds were elucidated by spectroscopic analyses, notably UV, MS and NMR.     

New dihydrochalcones and anti-platelet aggregation constituents from the leaves of Muntingia calabura

Two new dihydrochalcones, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone (1) and 4,2',4'-trihydroxy-3'-methoxydihydrochalcone (2), and a new flavanone, (2R,3R)-(-)-3,5-dihydroxy-6,7-dimethoxyflavanone (3), together with nineteen known compounds have been isolated from the leaves of Muntingia calabura. The structures of three new compounds were determined through spectral analyses including extensive 2D-NMR data. Among the isolates, 2,3-dihydroxy-4,3',4',5'-tetramethoxydihydrochalcone, 5,7-dihydroxy-3-methoxyflavone, 5,7-dihydroxy-6-methoxyflavone, 5,4'-dihydroxy-3,7-dimethoxyflavone, (2S)-7,8,3',4',5'-pentamethoxyflavan, (2S)-5'-hydroxy-7,8,3',4'-tetramethoxyflavan, and methyl gallate exhibited significant anti-platelet aggregation activity in vitro.