广东紫珠中的萜类化合物及其抗炎活性

对岭南药材广东紫珠(Callicarpa kwangtungensis)地上部分进行化学成分研究,得到11个萜类化合物,分别鉴定为sambucunlin A(1)、2α-羟基羽扇豆醇(2)、swinhoeic acid(3)、3β-羟基-乌苏烷-11-烯-13β,28-内酯(4)、蔷薇酸(5)、2α,3β,6β,18β,23-pentahydroxy-olean-12-en-28-oic acid(6)、rel-5-(3 S,8 S-dihydroxy-1 R,5 S-dimethyl-7-oxa-6-oxobicyclo-oct-8-yl)-3-methyl-2 Z,4 E-pentadienoic acid(7)、salvionoside B(8)、齐墩果酸(9)、白桦脂酸(10)和α-香树脂醇(11)。其中,化合物1~4和6~8为首次从该属植物中分离得到。在化学成分分离基础上,进一步选择脂多糖(LPS)诱导的RAW 264.7小鼠巨噬细胞炎症模型进行萜类化合物抗炎活性测试。结果表明:化合物3和9具有显著的抗炎活性,对比结构发现,三萜类化合物(3~6、9和11)抗炎活性优于倍半萜类化合物(7和8)。研究结果广东紫珠萜类成分在抗炎方面的临床应用提供了实验依据。     

Chemical Constituents from Fruits of Rosa davidii

From the fruit of Rosa davidii Crep., eleven compounds were isolated and identified by spectral evidence, viz. 2α,3β,19β-trihydroxyl-olean-12-en-28-oic acid (1), 2α,3β-dihydroxyl-urs-28(13)-lactone (2), arjunic acid (3), euscaphic acid (4), 2α,3β-dihydroxyl-urs-12-en-28-oic acid (5), oleanolic acid (6), kaempferol (7), tiliroside (8), quercetin (9), daucosterol (10) and β-sitosterol (11). Among them, 1 and 2 were new compounds.     

Antioxidant and alpha-amylase inhibitory compounds from aerial parts of Varthemia iphionoides Boiss

Various extracts of aerial parts of Varthemia (Varthemia iphionoides Boiss) were investigated for radical-scavenging activity, antioxidative activity, and porcine pancreas alpha-amylase inhibitory activity. The ethanol and water extracts showed a pronounced 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity, with inhibition of about 90% at a concentration of 100 microg/ml, and alpha-amylase inhibitory activity of about 70% at a concentration of 200 microg/ml by the 2-chloro-4-nitrophenyl alpha-maltotrioside (CNP-G3) degradation method. The ethanol extract was purified by column chromatography to give seven 3-methoxyflavones (1-7) and eudesmane sesquiterpene, selina-4,11(13)-dien-3-on-12-oic acid (8). The structures of these compounds were established by NMR, MS, and UV spectroscopy. Of 3-methoxyflavones, 5,7,4'-trihydroxy-3,6-dimethoxyflavone (1), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (2), and 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (3,7,3'-tri-O-methyl-quercetin) (7) exhibited pronounced radical-scavenging activity. The antioxidative activity in the linoleic acid system was considerable in compounds 1, 2, and 5,4'-dihydroxy-3,6,7-trimethoxyflavone (4). Compounds 1, 2, 4, 5 (5,7,4'-trihydroxy-3-methoxyflavone), and 6 (5,4'-dihydroxy-3,7-dimethoxyflavone) showed markedly high inhibitory activity against porcine pancreas alpha-amylase. Eudesmane sesquiterpene did not show any activity.     

Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities

To clarify the structural requirements of flavonoids for formation of advanced glycation end-products (AGEs), various flavonoids were examined. The results suggested the following structural requirements of flavonoids for the inhibition of AGEs formation: (1) as the hydroxyl groups at the 3′-, 4′-, 5-, and 7-positions increased in number, the inhibitory activities became stronger; (2) the activities of flavones were stronger than those of corresponding flavonols, flavanones, and isoflavones; (3) methylation or glucosylation of the 4′-hydroxyl group of flavones, flavonols, and flavanones reduced activity; (4) methylation or glycosylation of the 3-hydroxyl group of flavonols tended to increase activity; (5) glycosylation of the 7-hydroxyl group of flavones and isoflavones reduced activity. In addition, various flavonoids with strong AGEs formation inhibitory activity tended to exhibit strong scavenging activity for 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radicals, with several exceptions.     

裸花紫珠的化学成分

从裸花紫珠(Callicarpa nudiflora Hook.ex Arn.)地上部分的乙醇提取物中分离得到了7个化合物,经波谱分析确定其结构分别为:木犀草苷(1),木犀草素-3'-O-β-D-吡喃葡萄糖苷(2),木犀草素-4'-O-β-D-吡喃葡萄糖苷(3),2α,3α,19α-三羟基-乌索-12-烯-28-酸(4),乌索酸(5),2α-羟基-乌索酸(6)和齐墩果酸(7)。其中化合物2-7为首次从该植物中分离得到。     

肾茶化学成分的研究

从肾茶中分离得到11个已知化合物,通过NMR及MS数据分析,分别鉴定为：5-羟基-6,7,4’-三甲氧基黄酮（1）,5-羟基-6,7,3’,4＇-四甲氧基黄烷酮（2）,orthosipholF（3）,siphonolB（4）,白桦酯酸（5）,2α-羟基齐墩果酸（6）,2α,3α-二羟基-12-烯-28-齐墩果酸（7）,委陵菜酸（8）,蔷薇酸（9）,熊果酸（10）和胡萝卜甙（11）。其中,花合物2-9为首次从该植物中分离得到。     

肋果茶中的萜类化学成分研究

从肋果茶(Sladenia celastrifolia)95％乙醇提取物的乙酸乙酯部位中分离得到15个萜类化合物,经波谱学方法分别鉴定为sladeniafolin A(1),grasshopper ketone (2),(3S,5R,6S,7E,9R) -7-megastigmene-3,6,9-triol (3),hedytriol (4),(3S,5R,6R,7E,9R) -3,5,6,9-tetrahydroxy-7-megastigmene(5),1′S*,4′R*-8-(4′-hydroxy-2′,6′,6′-trimethylcyclohex-2-enyl)-6-methyloct-3E,5E,7E-trien -2-one (6),2α,3α,19α,23-tetrahydroxyurs-12-en-28-oic acid (7),2α,3β,19α,23-tetrahydroxyurs-12-en-28-oic acid(8),pomolic acid(9),3-O-acetyl pomolic acid(10),ursaldehyde (11),camarolide (12),3β-hydroxyurs-11-en-13β(28) -olide (13),3β-hydroxy -11α,12α-epoxy-urs-13β,28-olide (14)和28-0-β-D-glucopyranosyl euscaphic acid (15).以上化合物均首次从该植物中分离得到,其中1为新的C9裂环烯醚萜.     

Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots

The ethanolic root extract of Scrophularia lepidota, an endemic plant of the Turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-ACP reductase (FabI), a key enzyme of fatty acid biosynthesis in Plasmodium falciparum. Chromatographic separation of the extract yielded 10 iridoids (1-10), two of which are new, and a known phenylethanoid glycoside (11). The structures of the new compounds were determined as 3,4-dihydro-methylcatalpol (8) and 6-O-[4'-O-trans-(3,4-dimethoxycinnamoyl)-alpha-L-rhamnopyranosyl]aucubin (scrolepidoside, 9) by spectroscopic means. The remaining metabolites were characterized as catalpol (1), 6-O-methylcatalpol (2), aucubin (3), 6-O-alpha-L-rhamnopyranosyl-aucubin (sinuatol, 4), 6-O-beta-D-xylopyranosylaucubin (5), ajugol (6), ajugoside (7), an iridoid-related aglycone (10) and angoroside C (11). Nine isolates were active against Leishmania donovani, with the new compound 9 being most potent (IC50 6.1 microg/ml). Except for 4, all pure compounds revealed some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3-73.0 microg/ml). Only compound 10 showed moderate anti-plasmodial (IC50 40.6 microg/ml) and FabI enzyme inhibitory activity (IC50 100 microg/ml). 10 is the second natural product inhibiting the fatty acid biosynthesis of Plasmodium falciparum.     

Triterpenes and lignans from the leaves of Styrax tonkinensis

Two triterpenes (1 and 2) and eight lignans (3–10) were isolated from the ethyl acetate-soluble fraction of the leaves of Styrax tonkinensis (Pierre) Craib ex Hartw (Styracaceae). Their structures were established as ursolic acid (1), pomolic acid (2), 3,3′-bis(3,4-dihydro-6-methoxy-2H-1-benzopyran) (3), rac-(8α,8′β)-4,4′-dihydroxy-3,3′-dimethoxylignan-9,9′-diyldiacetate (4), (-)-secoisolariciresinol (5), (+)-pinoresinol (6), 4,4′-dihydroxy-3,3′-dimethoxy-9-ethoxy-9,9′-epoxylignan (7), (2S,3R, 4R)-4-[1-ethoxy-1-(4-hydroxy-3-methoxy)phenyl]methyl-2-(4-hydroxy-3-methoxy)phenyl-3-hydroxymethyl-tetrahydrofuran (8), (-)-neo-olivil-(9-O-9″)-seco-isolariciresinol (9) and isolariciresinol (10) based on MS, ¹H-and ¹³C-NMR spectral data. All these compounds (1–10) were firstly isolated from this plant, and compounds 2–5 and 7–9 were reported from the Styrax genus for the first time. Furthermore, the chemotaxonomic significance of the isolated compounds was discussed.     

Six New Constituents from the Fruit of Hypericum patulum and Their Anti-Inflammatory Activity

Four new xanthone glucosides, 3-hydroxy-2-methoxyxanthone-4-O-β-D-glucopyranoside ( 1 ), 4,8-dihydroxy-2-methoxyxanthone-3-O-β-D-glucopyranoside ( 2 ), 2-methoxyxanthone-5-O-β-D-glucopyranoside ( 3 ), 4-hydroxy-2-methoxyxanthone-3-O-β-D-glucopyranoside ( 4 ), a new phenolic acid, 4,4′-dihydroxy-3,3′-imino-di-benzoic acid monomethyl ester ( 5 ), and a new isoquinoline, methyl 6-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate ( 6 ) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR-ESI-MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. Compound 2 , 3 exhibited moderate inhibitory activity against NO production.     

Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and evaluation as inhibitors of steroid-5alpha-reductase type 1 and 2

The synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) is described [benzoyl (1), benzyl (2), adamantanoyl (3), cyclohexanoyl (4), cyclohexylacetyl (5), diphenylacetyl (6), dicyclohexylacetyl (7), 2-propylpentanoyl (8), diphenylcarbamoyl (9), trimethylacetyl (10), 3,3-dimethylacryloyl (11), dicyclohexylacetyl derivative of the benzyl compound (12)]. Compounds were tested for inhibitory activity toward 5alpha-reductase isozymes 1 and 2 in human and rat. The test compounds inhibited 5alpha-reductase, showing a broad range of inhibitory potencies. In rat, compounds 6 (IC50 = 3.44 and 0.37 microM for type 1 and 2, respectively) and 9 (IC50=0.54 and 0.69 microM for type 1 and 2, respectively) displayed the best inhibition toward both isozymes. Compound 7 showed a strong inhibition toward type 2 human and rat enzyme (IC50 = 60 and 80 nM) but only a moderate activity versus type 1 enzyme (IC50 approximately 10 microM for rat and human enzyme). In vivo, selected compounds reduced prostate weights in castrated testosterone treated rats.     

Aldose reductase inhibitors from the leaves of Myrciaria dubia (H. B. & K.) McVaugh

Ellagic acid (1) and its two derivatives, 4-O-methylellagic acid (2) and 4-(alpha-rhamnopyranosyl)ellagic acid (3) were isolated as inhibitors of aldose reductase (AR) from Myrciaria dubia (H. B. & K.) McVaugh. Compound 2 was the first isolated from the nature. Compound 3 showed the strongest inhibition against human recombinant AR (HRAR) and rat lens AR (RLAR). Inhibitory activity of compound 3 against HRAR (IC50 value = 4.1 x 10(-8) M) was 60 times more than that of quercetin (2.5 x 10(-6) M). The type of inhibition against HRAR was uncompetitive.     

Inhibitory effect of some acetyl esters and acetamides on glycation of the histone H1

Non-enzymatic glycosylation (glycation) is a spontaneous set of reactions between reducing sugars and free amino groups in proteins or other biomolecules leading to the formation of fluorescent and coloured compounds known as advanced glycation end products (AGEs). AGEs cause structural changes of key proteins in humans, and therefore they are related with a number of physiological processes and diseases such as aging, atherosclerosis, cataract, arthritis, Alzheimer's disease. Two main strategies have been employed to prevent the formation of AGEs: a) low carbohydrate diet and b) pharmacological intervention. The latter includes treatment with reactive compounds which might be either sugar competitors (type A), carbonyl traps (type B) or free radical trapping antioxidants (type C). Acetylsalicylic acid (ASA, aspirin) is a good example of sugar competitor capable of inhibiting glycation by acetylating epsilon-amino groups of lysine residues in proteins. Taking into consideration the inhibiting effect of ASA on glycation we designed to study the antiglycation activity of other acetyl group-containing compounds (acetamides and acetyl esters) using the lysine-rich protein histone H1 as a model. The glycation of the histone H1 was carried out by either fructose or a complex mixture of glycating agents obtained from E. coli and monitored by fluorescent spectroscopy, SDS-PAGE and measurement of the content of reactive carbonyl groups in the target protein. Our results showed that the inhibitory effect of phenyl acetate, acetanilide, 4-acetamidophenylacetic acid and isopropenyl acetate was comparable to that of ASA. Based on the obtained results we conclude that these compounds act as free radical scavengers protecting proteins from the damaging effect of reactive oxygen species produced during the formation of AGEs.     

黔产青钱柳化学成分及α-葡萄糖苷酶抑制活性研究

为了阐明青钱柳中的降血糖功效成分,实验对黔产青钱柳进行了系统化学成分研究和α-葡萄糖苷酶抑制活性评价。利用各种色谱学手段和波谱学方法,从青钱柳叶80%乙醇提取物中分离鉴定出13个化合物,分别为阿福豆苷(1)、山柰酚3-O-(4″-O-乙酰基)-α-L-吡喃鼠李糖苷(2)、juglanoside J(3)、1α,2α,4β-3羟基-1,2,3,4-四氢萘酮(4)、青钱柳苷III(5)、青钱柳苷J(6)、黄体酮(7)、去酰基萝藦苷元(8)、20-乙酰氧基-4-烯-3-酮(9)、齐墩果酸(10)、5-O-P香豆酰奎宁酸甲酯(11)、亚麻酸甲酯(12)、软脂酸(13)。其中,化合物9为新天然产物,化合物2~4、7、8、11、13均为首次从该植物中分离得到。用PNPG法对化合物1~10进行了α-葡萄糖苷酶抑制活性筛选,结果显示,化合物1、2有较强的α-葡萄糖苷酶抑制活性,表明黄酮类成分是青钱柳降血糖功效的物质基础之一。     

Prolyl endopeptidase inhibitors from Syzygium samarangense (Blume) Merr. & L. M. Perry

Compounds isolated from the hexane extract of the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry were tested for inhibitory activity against the following serine proteases: trypsin, thrombin and prolyl endopeptidase. The compounds were identified as an intractable mixture of alpha-carotene and beta-carotene (1), lupeol (2), betulin (3), epi-betulinic acid (4), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (5), 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (7), 2',4'-dihydroxy-6'-methoxy-3'-methyldihydrochalcone (8) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (9). Hydrogenation of compounds 5, 6 and 7 yielded compound 8, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (10) and 2',4'-dihydroxy-6'-methoxy-3',5'-dimethyldihydrochalcone (11), respectively. The hydrogenated products of compounds 6 and 7 were also tested for enzyme inhibitory activity. In addition, beta-sitosterol (12) and beta-D-sitosterylglucoside (13) were also isolated. This is the first report of the isolation of compounds 1-6, 8 and 13 from this plant. Compounds 3-8 and 10 exhibited significant and selective inhibition against prolyl endopeptidase among three serine proteases. This is the first report of this kind of activity for all these compounds.     

海南蕊木枝叶生物活性成分研究

从海南蕊木(Kopsia hainanensis Tsiang)枝叶的乙醇提取物中分离得到7个化合物,通过波谱分析(NMR、MS、IR等),鉴定其结构分别为:蕊木宁(1)、土波台文碱(2)、二氢脱氢二松柏基醇(3)、 β-香树脂醇(4)、熊果酸(5)、 2α,3β-二羟基熊果酸(6)和 β-谷甾醇(7)。其中化合物3~7为首次从该植物中分离得到。用滤纸片琼脂扩散法检测表明,化合物1~3和5对耐甲氧西林金黄色葡萄球菌(MRSA)生长有抑制作用;化合物2对金黄色葡萄球菌生长有抑制作用;化合物5对慢性髓原白血病细胞(K562)、人胃癌细胞(SGC-7901)和人肝癌细胞(SMMC-7721)增殖均具有细胞毒活性。     

Polyphenols from flowers of Magnolia coco and their anti-glycation effects

We investigated the inhibitory effects of several plant extracts on advanced glycation end-products (AGEs) formation. Among tested samples, the flower extract of Magnolia coco showed significant inhibition of AGE formation. We isolated and characterized procyanidin oligomer and four other compounds from the flowers, and evaluated their inhibitory effects on AGE formation and the AGE-derived crosslink-cleaving activity of the isolated compounds.     

Synthesis of aminooxy-functionalized lanthanide(III) chelates for carbonyl-group conjugation

The syntheses of three new aminooxy-tethered lanthanide(III) chelates, compounds 1-3, incorporating DOTA (= 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), DTPA (= diethylenetriaminepentaacetic acid), or a substituted terpyridine (2,2',2',2'-[2,2': 6',2'-terpyridine-6,6'-diylbis(methylenenitrilo)]tetraacetic acid), respectively, are described. Reagents 1-3 can be used for carbonyl 'labeling', as shown by the formation of the corresponding oxime-ether bioconjugates of naltrexone (16) and 2-deoxy-beta-D-glucose (17) (Scheme 4).     

内生真菌Paraconiothyrium brasiliense代谢产物β-咔啉生物碱及其黄嘌呤氧化酶抑制活性研究

本研究通过前体介导调控一株内生真菌的次级代谢产物,采用正相硅胶柱色谱和制备型HPLC等方法分离纯化,利用NMR、MS等波谱学方法鉴定化合物结构,从中分离鉴定了10个生物碱类化合物,鉴定结果为:川芎哚(1)、1-(1',2'-二脱氧-α-D-核吡喃糖基)-β-咔啉(2)、flazin(3)、tangutorid E(4)...     

Anti-cancer and immunostimulatory activity of chromones and other constituents from Cassia petersiana

Phytochemical investigation of Cassia petersiana Bolle leaves afforded four new compounds, including two chromone derivatives, 7-acetonyl-5-hydroxy-2-methylchromone (petersinone 1, 1) and 7-(propan-2'-ol-l'-yl)-5-hydroxy-2-methylchromone (petersinone 2, 2), two benzoic acid derivatives, 5-methyl-3-(propan-2'-on-1'-yl) benzoic acid (petersinone 3, 3) and 5-(methoxymethyl)-3-(propan-2'-ol-1'-yl) benzoic acid (petersinone 4, 4), and glyceryl-1-tetracosanoate (6), in addition to the known compound sistosterol-3-beta-D-glycoside (5). The structures of these compounds were determined by comprehensive NMR studies, including DEPT, COSY, HMQC, HMBC, MS and IR. Compounds 1, 2, 5 and 6 were tested for antioxidant, anti-cancer and immunostimulatory properties. The biological investigations indicated that compound 6, among others, possessed the highest anti-cancer activity against hepatocellular carcinoma, immunoproliferative activity via induction of T-lymphocytes and macrophage proliferation, anti-inflammatory activity as indicated by NO inhibition, and antioxidant activity against DPPH radicals. Moreover, compound 5 was the most effective cytotoxic compound against breast carcinoma and stimulated a consistent immunoproliferative effect on lymphocytes and macrophages combined with strong NO inhibitory activity, while compound 1 was promising as immunoproliferative agent and may act as anti-inflammatory agent as a consequence of its NO inhibitory activity.