Phytochemistry and preliminary biological evaluation of Cyathostemma argenteum, a malaysian plant used traditionally for the treatment of breast cancer

Bioassay guided fractionation of the roots of Cyathostemma argenteum using the brine shrimp resulted in the isolation of two uncommon flavanones, 2,5-dihydroxy-7-methoxy flavanone 1 and 2,5-dihydroxy-6,7-dimethoxy flavanone 2 while the stem bark yielded the related compounds 5-hydroxy-7-methoxy flavone 3 and 5-hydroxy-6,7-dimethoxy flavone 4. The alkaloids liriodenine 5 and discretamine 6 as well as benzyl benzoate 7 were isolated from the roots and 6 was also isolated from the stembark. In cytotoxicity tests using four human breast cancer cell lines, 1 and 2 were weakly toxic to MCF-7 cells (IC(50) = 19.6 and 19.0 microM, respectively) but showed little activity against MCF-7 cells resistant to doxorubicin or against two oestrogen receptor-deficient cell lines. Compound 5, but not 6 and 7, was moderately cytotoxic against all four cell lines. These results are discussed in the context of the traditional use of C. argenteum in the treatment of breast cancer.     

厚果鸡血藤种子中的一个新异戊烯基查耳酮(英文)

目的:研究厚果鸡血藤种子的化学成分。方法:采用硅胶、MCI等多种层析柱分离手段.运用NMR和MS等波谱技术鉴定化合物的结构。结果:从厚果鸡血藤种子中分离并鉴定了4个黄酮类化合物:3-hydroxy-4-methoxylonchocarpin(1),4-methoxylonchocarpin(2),isobavachromene(3),dorspoinsettifolin(4)。结论:化合物1为新的查耳酮,化合物2-4为首次从该属植物中分离得到;化合物1-4对测试的部分细胞株显示了中等的抑制活性。     

Bioactivity‐guided Isolation of Cytotoxic Sesquiterpene Lactones of Gochnatia polymorpha ssp. floccosa

Phytochemical study of Gochnatia polymorpha (Less) Cabr. ssp. floccosa Cabr. trunk bark, guided by antiproliferative assays on 10 human cancer cell lines and the VERO cell line, yielded six known compounds identified as the triterpene bauerenyl acetate, the guaianolide 11α,13‐dihydrozaluzanin C and the dimeric guaianolides 10‐desoxygochnatiolide A, gochnatiolide A, 8‐hydroxi‐10‐desoxygochnatiolide A and 8‐hydroxigochnatiolide A. Extracts, fractions of extracts and isolated compounds were tested in vitro against a panel of human cancer cell lines, including U251 (glioma, CNS), UACC‐62 (melanoma), MCF‐7 (breast), NCI‐ADR/RES (drug‐resistant ovarian), 786.0 (kidney), NCI‐H460 (lung, no small cells), PC‐3 (prostate), OVCAR‐3 (ovarian), HT‐29 (colon), K562 (leukemia) and against the VERO no cancer cell line. Bauerenyl acetate was inactive, while 11α,13‐dihydrozaluzanin C showed weak activity against UACC62 and the VERO cell line. The most active compounds were 10‐desoxygochnatiolide A and gochnatiolide A, which inhibited the growth of kidney, melanoma, ovarian‐resistant and glioma cell lines with values of TGI (total growth inhibition) varying 0.21–1.09 µg/mL. This is the first report about cytotoxic activity of dimeric lactones against cell lines. Copyright © 2011 John Wiley & Sons, Ltd.     

Cytotoxic principles from Ventilago leiocarpa

Three new anthraquinones, islandicin 4-methyl ether (1), 1,2,6-trihydroxy-7,8-dimethoxy-3-methylanthraquinone (2), and 2-hydroxyemodin 1-methyl ether (3) as well as two known triterpenoids [taraxerol (4), lupeol (5)], six anthraquinones [chrysophanol (6), islandicin (8), parietin (9), emodin (10), catenarin (11), skyrin (15)], a 2,3-dihydroflavonol [(+)-aromadendrin (12)], two benzisochromanquinones [ventiloquinone K (13) and ventiloquinone I (14)], and stigmasterol (7) were isolated from Ventilago leiocarpa. The cytotoxicity of these compounds to various tumor cell lines was evaluated, and compound 15 significantly suppressed growth of HeLa, Vero, K562, Raji, Wish, and Calu-1 tumor cell lines. With the exception of K562 cells, the proliferation of other tumor cell lines was inhibited by compounds 3 and 10.     

Cytotoxic 3,20-epoxy-ent-kaurane diterpenoids from Isodon eriocalyx var. laxiflora

Four new ent-kaurane diterpenoids, laxiflorins J-M (1-4), along with maoecrystal A (5) and maoecrystal P (6), were isolated from the leaves of Isodon eriocalyx var. laxiflora. Their structures were determined by spectroscopic analyses. All the compounds were assayed for their cytotoxic effects on human tumor K562, A549, and T24 cell lines. Compounds 1 and 6 showed significant inhibitory effects on human tumor K562 and T24 cells, with IC(50) values less than 0.5 microg/mL. Compound 3 also demonstrated cytotoxic activities against all three types of human tumor cells, with IC(50) values in the range of 1-25 microg/mL.     

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??OBJECTIVE To study the anti-cancer components of Calotropis gigantean L.METHODS The powdered whole plants of C. gigantea were extracted with 95% alcohol. After removal of the solvent, the residue was extracted with petroleum ether and chloroform, and the compounds in the chloroform extract were isolated and purified by different column chromatograghies carried out on silica gel, RP-18, MCI, and Sephadex LH-20 and their structures were elucidated by spectral data. RESULTS Thirteen compounds were isolated and their structures were characterized as gofruside(1), uzarigenin(2), arjunolic acid(3), 3??-(1??-hydroxyethyl)-7-hydroxy-1-isobenzofuranone(4), daucosterol(5), syringaresinol(6),12-O-benzoyl-deacylmetaplexigenin(7), 3-hydroxy-4-methoxybenzoic acid(8), oleanolic acid(9),??-sitosterol(10), methyl 1-naphthaleneacetate(11), butylparaben(12),??-D-oleandropyranoside(13), and compounds 2-4,6-9, and 11-13 were isolated from this plant for the first time. Compounds 1 and 2 showed cytotoxicity against HLE, K562, RPMI8226, MCF7, MDA, and WM9 cell lines, with K562 and RPMI8226 being the most sensitive cells.CONCLUSION Compounds 1 and 2 are premilinarily judged as the anti-cancer components in C. gigantean.     

Isolation, structure elucidation, and cytotoxic evaluation of furanonaphthoquinones from in vitro plantlets and cultures of Streptocarpus dunnii

Two new furanonaphthoquinones, (3R)-7-methoxy-α-dunnione (5) and (3R)-6-hydroxy-7-methoxy-α-dunnione (6), along with the known (3R)-dunnione (1), (3R)-α-dunnione (2), (3R)-7-hydroxy-α-dunnione (3), and 1-hydroxy-2-methylanthraquinone (4), were isolated from in vitro cultures of Streptocarpus dunnii. The structures of compounds 5 and 6 were established by spectroscopic means. This is the first report of hydroxylated furanonaphthoquinones in a Streptocarpus species. Compounds 1-3 demonstrated cytotoxic activity against a range of breast cancer and pancreatic tumor cell lines.     

New isoprenylated flavones, artochamins A--E, and cytotoxic principles from Artocarpus chama

Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known flavones (6-13), were isolated from the roots of Artocarpus chama. All structures were elucidated by spectroscopic methods. Artonin E (12) showed strong cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231 (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN) variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects compared with 3 and 12.     

Cytotoxic flavonol glycosides from Triplaris cumingiana

Three new compounds, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl-4,6-bis-O-beta-D-(3,4,5-trihydroxybenzoyl)glucopyranoside (1), 5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-3-yl-5-O-alpha-L-(3,4,5-trihydroxybenzoyl)arabinofuranoside (2), and 2-hydroxy-4-O-alpha-L-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenylarabinofuranoside (3), were isolated from the young leaves of Triplaris cumingiana, together with two known compounds, quercetin 3-O-alpha-L-(5"-O-galloyl)arabinofuranoside (4) and quercetin 3-O-beta-D-(6"-O-galloyl)glucopyranoside (5). The structures of 1-3 were established by spectroscopic methods. Compounds 1-5 were evaluated for their cytotoxic activities against the MCF-7, H-460, and SF-268 human cancer cell lines.     

Triterpenes from Garcia parviflora. Cytotoxic evaluation of natural and semisynthetic friedelanes

Three new friedelane-type triterpenes, 1,2-dehydro-2,3-secofriedelan-3-oic acid (1), 1β-hydroxyfriedelin (2), and 3β-hydroxyfriedelan-23-oic acid (3), and the known compounds friedelin-3,4-lactone (4), acetyl aleuritolic acid (5), 4-hydroxy-5-propionyl-1,3-di-O-methylpyrogallol, elemicin, and (-)-syringaresinol were isolated from the leaves of Garcia parviflora. The structures of 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR, HREIMS, X-ray, and CD analysis. Some derivatives of 2 (6-14) were prepared via oxidation, reduction, and esterification. The natural triterpenes and the semisynthetic friedelane derivatives were tested for cytotoxic activity against human cancer cell lines U251, PC-3, K562, HCT-15, MCF-7, and SKLU-1. Compound 5 was cytotoxic against U251 cells.     

Isolation and structure elucidation of a new potent anti-neoplastic diterpene from Dendrostellera lessertii

Two diterpene esters were isolated from Dendrostellera lessertii. These compounds were identified as compound I (12-O-benzoyl-3,5-hydroxy-6,7-epoxy-resiniferonol-9,13,14-orthobenzoate) and compound 11 (12-O-benzoyl-5-hydroxy-6,7-epoxy-resiniferonol-9,13,14-orthodecanoate). Cytotoxicity evaluation of these two compounds, using seven different cancerous cell lines, indicated that compound I with IC50 of 5-25 nmol, is 2.5 times more active than compound II. Using flow cytometry technique, it was found that treatment of the most responsive cells (K562) with compound I inhibited the progression of cells through G1 phase by almost 20% compared to the untreated cells.     

Antiproliferative properties of polyketides isolated from Virola sebifera leaves

An activity-guided fractionation of Virola sebifera Aubl. methylene chloride-soluble fraction provided novel 3,5-dihydro-2-(1'-oxo-3'-hexadecenyl)-2-cyclohexen-1-one (3), two known lignans (1, 2) and dehydro hexadecanoyl resorcinol (4). Isolation and purification were conducted with the application of column chromatography and structures were assigned by spetral analysis (1D and 2D NMR, HREIMS). Compounds 1-4 were evaluated for cytotoxic activities against human tumour cell lines UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal) and NCI-ADR (breast expressing phenotype multiple drugs resistance) in vitro. The new polyketide (3) showed selectivity against human OVCAR03 and NCI-ADR cell lines, ranging from 2 to 4 microg/mL.     

Terpenoids and norlignans from Metasequoia glyptostroboides

Four new terpenoids, metaseglyptorin A (1), metasequoic acid C (2), 12α-hydroxy-8,15-isopimaradien-18-oic acid (3), and (-)-acora-2,4(14),8-trien-15-oic acid (4), and three new norlignans, metasequirins D-F (5-7), were isolated from Metasequoia glyptostroboides, together with 15 known compounds. Structures of the new compounds were determined by analysis of their spectroscopic data, and the absolute configuration of 7 was established by the modified Mosher method. All of the compounds were evaluated for cytotoxicity against five human tumor cell lines.     

浅裂鳞毛蕨地上部分二氢黄酮类化学成分研究

 目的对鳞毛蕨属植物浅裂鳞毛蕨(Dryopteris sublaeta Ching et Hsu.)地上部分的化学成分进行研究。方法利用硅胶柱色谱进行分离纯化,根据化合物的理化性质和光谱数据鉴定结构。结果浅裂鳞毛蕨地上部分用体积分数为70%丙酮提取液乙醚萃取部位分离得到了5个化合物,分别鉴定为:(2S)5,7-二羟基-6,8-二甲基二氢黄酮(去甲氧基荚果蕨素)(Ⅰ),(2S)5,7-二羟基-6,8-二甲基-4′-甲氧基二氢黄酮(荚果蕨素)(Ⅱ),(2S)5,7,2′-三羟基-6,8-二甲基-二氢黄酮(Ⅲ),(2S)5,7,4′-三羟基-3′-甲氧基-6,8-二甲基二氢黄酮(Ⅳ),(2S)5-羟基-4′-甲氧基-6,8-二甲基二氢黄酮-7-O-β-D-葡萄糖苷(Ⅴ)。结论上述5个二氢黄酮类化合物均为首次从浅裂鳞毛蕨地上部分中分离得到。     

Triterpenoids from the floral spikes of Betula platyphylla var. japonica and their reversing activity against multidrug-resistant cancer cells

Four new triterpenes, together with 16 known triterpenes, were isolated from the floral spikes of Betula platyphylla var. japonica in a search for compounds capable of reversing multidrug resistance in cancer cells. The structures of the new triterpenes were elucidated as 3,4-seco-olean-4(23),13(18)-dien-3-oic acid (1), 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (2), 3-O-methylmalonylepiocotillol II (6), and 3-O-methylmalonylcabraleahydroxylactone (16) by spectroscopic examination. The cytotoxicity of the isolated triterpenes against human cancer cell lines as well as multidrug-resistant cancer cell lines was evaluated. Most of the isolated triterpenes showed very weak cellular toxicities. Although no discernible differences were found in the cytotoxicities for the tested compounds against sensitive and resistant cell lines, the cytotoxicities for several triterpenes against multidrug-resistant cancer cell lines (KB-C2 or K562/Adr) were enhanced in the presence of nontoxic concentrations of colchicine or doxorubicin. Compound 10 reversed the cytotoxicity of colchicine against KB-C2 cells at 8.1 microM and showed comparable potency to 5 microM verapamil.     

Antihyperglycemic activity and chemical constituents of Eysenhardtia platycarpa

The methanolic extracts from branches (BEP) and leaves (LEP) of Eysenhardtia platycarpa significantly decreased the blood glucose levels in normal and streptozotocin (STZ)-induced diabetic rats. One new flavone, (1"R)-5,4',1"-trihydroxy-6,7-(3",3"-dimethylchroman)flavone (1), together with the known compounds 5,7-dihydroxy-6-methyl-8-prenylflavanone (3), 5,7-dihydroxy-8-methyl-6-prenylflavanone (4), 5,7-dihydroxy-6-prenylflavanone (5), 5,7-dihydroxy-8-prenylflavanone (6), 3-O-acetyloleanolic acid (7), oleanolic acid, 3beta-acetoxy-11alpha,12alpha-epoxy-oleanan-28,13beta-olide, lupeol, betulinic acid, beta-sitosterol, beta-sitosteryl beta-D-glucopyranoside, beta-sitosteryl palmitate, and 3-O-methyl-myo-inositol were isolated from BEP. Additionally, one new flavanone, (2S)-4'-O-methyl-6-methyl-8-prenylnaringenin (2), as well as the known compounds 3, 4, 6, 4'-O-methyl-8-prenylnaringenin (8), and 5-hydroxy-7-methoxy-8-prenylflavanone (9) were isolated from LEP. 3-O-Acetyloleanolic acid (7), identified as the major constituent of BEP, showed a significant decrease (31 mg/kg of body weight, P < 0.05) in the glucose level of STZ-induced diabetic rats. The obtained results correlate with the traditional use of this species.     

4-氨基-2-三氟甲基喹唑啉衍生物的合成及其体外抗肿瘤活性研究

目的 基于喹唑啉为母核设计发现新型抗肿瘤活性化合物。方法 以邻氨基苯甲酰胺和三氟乙酸酐为起始原料采用缩合、环化、氯代和偶联反应等合成了一系列4-氨基-2-三氟甲基喹唑啉衍生物(5a~5u)。采用四甲基偶氮唑盐(MTT)法评价所得目标化合物对人肺癌细胞A549、人宫颈癌细胞Hela、人白血病细胞K562、人前列腺癌细胞PC-3、人前列腺癌细胞LNCaP这5种肿瘤细胞的体外增殖抑制活性。结果 化合物5c在5 μmol·L^-1时对PC-3肿瘤细胞的抑制率为49.3%,化合物6a对LNCaP和K562、以及6b对PC-3的抑制率超过了50.0%。结论 本实验设计合成的4-氨基-2-三氟甲基喹唑啉类化合物多数具有一定的抗肿瘤活性,特别是4-氨基的N-甲基化产物6a、6b的体外抗肿瘤活性较原型化合物(5n与5u)显著增强,为该类化合物的进一步研究提供参考。     

Cytotoxic lignans from the stem bark of Magnolia officinalis

Three new lignans, 4'-methoxymagndialdehyde ( 1), 4'-methoxymagnaldehyde B ( 2), and 4'-methoxymagnaldehyde E ( 3), were isolated from hexane- and EtOAc-soluble fractions of the stem bark of Magnolia officinalis, together with eight known compounds ( 4- 11). The structures of compounds 1- 3 were determined on the basis of spectroscopic and physicochemical data analysis. Compounds 1- 11 were tested in vitro for their cytotoxic activity against the K562, HeLa, and A549 cancer cell lines. Among the compounds tested, compound 1 showed the most potent cytotoxic activity against these cancer cell lines, with IC50 values of 3.9, 1.5, and 3.7 microg/mL, respectively.     

Cytotoxic flavonoids with isoprenoid groups from Morus mongolica.

A new pyranoflavanone, sanggenol L (1), a Diels-Alder type adduct regarded as a cycloaddition product of a dehydrogeranylflavanone and a prenylchalcone, sanggenol M (2), along with four new 2-arylbenzofurans with isoprenoid units, mulberrofurans W-Z (3-6), were isolated together with 10 known flavonoids from Chinese Morus mongolica. The structures of these novel compounds were elucidated by spectroscopic methods. All flavanones investigated here showed higher cytotoxicity against human oral tumor cell lines (HSC-2 and HSG) than against normal human gingival fibroblasts (HGF). Among them, the cytotoxicity of compound 2 and the Diels-Alder type flavanone sanggenon C (7) isolated from Morus cathayana were the most potent. On the other hand, seven 2-arylbenzofurans exhibited lower cytotoxicity and tumor specificity as compared with flavanones.     

Aromatase inhibitors from Broussonetia papyrifera.

Bioassay-guided fractionation of an ethyl acetate-soluble extract from the whole plants of Broussonetia papyrifera, using an in vitro aromatase inhibition assay, led to the isolation of five new active compounds, 5,7,2',4'-tetrahydroxy-3-geranylflavone (1), isogemichalcone C (8), 3'-[gamma-hydroxymethyl-(E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate (9), demethylmoracin I (10), and (2S)-2',4'-dihydroxy-2' '-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanone (11), and 10 known (12-21) compounds which were also found to be active. Of these compounds, the most potent were 9 (IC(50) 0.5 microM), 11 (IC(50) 0.1 microM), isolicoflavonol (12, IC(50) 0.1 microM), and (2S)-abyssinone II (13, IC(50) 0.4 microM). Additionally, six new compounds, 5,7,3',4'-tetrahydroxy-6-geranylflavonol (2), 5,7,3',4'-tetrahydroxy-3-methoxy-6-geranylflavone (3), (2S)-7,4'-dihydroxy-3'-prenylflavan (4), 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propane (5), 1-(2,4-dihydroxy-3-prenylphenyl)-3-(4-hydroxyphenyl)propane (6), and 1-(4-hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane (7), were isolated and characterized, but proved to be inactive as aromatase inhibitors, as were an additional 21 known compounds. The structures of the new compounds (1-11) were elucidated by spectroscopic methods. Structure-activity relationships in the aromatase assay were determined for the benzofurans, biphenylpropanoids, coumarins, and various types of flavonoids (chalcones, flavans, flavanones, and flavones) obtained among a total of 42 constituents of B. papyrifera.