Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii, and structure anti-HIV activity relationships of Tripterygium alkaloids

Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.     

茶藤生物碱成分的分离鉴定及抗肿瘤活性研究

目的 对茶藤Melodinus magnificus的生物碱成分进行分离、鉴定和抗肿瘤活性研究。方法 采用薄层色谱、柱色谱等色谱方法对总生物碱浸膏进行分离和纯化。通过ESI-MS、¹H-NMR、¹³C-NMR等波谱技术和文献对比等方法鉴定生物碱化合物的结构,并采用MTT法对分离得到的生物碱化合物进行抗肿瘤细胞(人肝癌HepG2细胞、乳腺癌MCF7细胞和人肺癌A549细胞)活性筛选,随后利用网络药理学和分子对接技术对具有抗肿瘤活性生物碱化合物的潜在靶点和作用通路进行预测。结果 从茶藤枝叶总生物碱中共获得10个化合物,分别鉴定为strictamine(1)、deacetylakuammiline(2)、19-(Z)-akuammidine(3)、14,15-didehydrovincamine(4)、14,15-didehydro-16-epi-vincamine(5)、19-(S)-methoxytubotaiwine(6)、19-(R)-methoxytubotaiwine(7)、rhazimine(8)、rhazicine N^4<...     

Plant antitumor agents, 19. Novel triterpenes from Maprounea africana

Four new pentacyclic triterpenes have been isolated from Maprounea africana. These triterpenes are members of the previously unknown urs-12-en-29-oic acid series. The structures of these compounds were deduced from spectral and chemical evidence. The parent compound, maprounic acid, was identified as 3B-hydroxyurs-12-en-29-oic acid. The remaining three triterpenes were identified as maprounic acid 3-p-hydroxybenzoate, 7 beta-hydroxymaprounic acid 3-p-hydroxybenzoate, and 2 alpha-hydroxymaprounic acid 2,3-bis-p-hydroxybenzoate. Of the four triterpenes, only the 7 beta-hydroxy derivative exhibited in vivo P-388 activity.     

Plant antitumor agents, 21. Flavones, coumarins, and an alkaloid from Sargentia greggii

Investigation of the MeOH extracts of Sargentia greggii (Rutaceae) led to the isolation of two known flavones, zapotin and 5,6,2'-trimethoxyflavone, and a new flavone, 5,6,2',3',4',6'-hexamethoxyflavone (1), whose structure was established by spectral data and confirmed by total synthesis. In addition, two known coumarins, 3-(alpha,alpha-dimethylallyl) herniarin and seselin, and a new coumarin, O-geranylosthenol (3), have been isolated from this plant. The structure of 3 was deduced from spectral data. Although the crude extracts displayed KB activity, none of the crystalline compounds were significantly active.     

Plant antimutagenic agents, 5. Isolation and structure of two new isoflavones, fremontin and fremontone from Psorothamnus fremontii

Two new isoflavones, fremontin and fremontone, were isolated from roots of Psorothamnus fremontii (Fabaceae), a desert plant. Compound 1 has the structure 5'-(alpha, alpha-dimethylallyl)-5,7,2',4'-tetrahydroxyisoflavone; compound 2 is similar but also contains the 3'-(gamma,gamma-dimethylallyl) substituent. The alpha,alpha-dimethylallyl substituent is rarely observed, and the combination of the alpha,alpha- and gamma,gamma-dimethylallyl substituents is unprecedented. Both 1 and 2 were nontoxic toward Salmonella typhimurium and were both highly active in the inhibition of mutagenicity of ethyl methanesulfonate (EMS) at all concentrations tested. Compound 2 was more active than 1 in the inhibition of mutagenicity of 2-aminoanthracene (2AN) and acetylaminofluorene (AAF) toward S. typhimurium.     

Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata

Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.     

Antineoplastic agents, 195. Isolation and structure of aceratioside from Aceratium megalospermum

A new tetralin glucoside [1], named aceratioside, has been found to be a weakly cytostatic (PS ED50 9 micrograms/ml) constituent in leaves produced by the Australian rain forest tree Aceratium megalospermum. Structural determination of aceratioside was primarily accomplished with results from a series of acetylation, methylation, and high field nmr (including heteronuclear multiple bond correlation) experiments.     

Macrophyllionium and macrophyllines A and B, oxindole alkaloids from Uncaria macrophylla

An unusual oxindole alkaloid inner salt, macrophyllionium (1), and a pair of new tetracyclic oxindole alkaloids, macrophyllines A (2) and B (3), together with six known alkaloids, were isolated from the aerial parts of Uncaria macrophylla. Corynantheidine (8) exhibited moderate cytotoxicity against HL-60 and SW480 cells with IC(50) values of 13.96 and 23.28 μM, respectively. Dihydrocorynantheine (9) exhibited significant vasodilating activity against phenylephrine-induced contraction in rat thoracic aorta rings (IC(50) = 6.73 μg/mL). In addition, compounds 2, 6, and 9 showed weak inhibitory action on KCl-induced contraction.     

小叶臭黄皮咔唑生物碱化学成分及其抗肿瘤活性研究

目的研究小叶臭黄皮Clausena excavate根的化学成分及抗肿瘤活性。方法采用硅胶、RP-18和HPLC等色谱技术分离纯化,根据理化常数和波谱数据鉴定化合物的结构,采用SRB法测定化合物1、2、7、8、10的细胞毒活性。结果从小叶臭黄皮根的甲醇提取物中分离得到13个咔唑生物碱,分别鉴定为2,3-二甲氧基-3-羧基咔唑生物碱(1)、1-羟基-3-甲酸甲酯咔唑生物碱(2)、7-羟基-3-醛基咔唑生物碱(3)、2,7-二甲氧基-3-甲酸甲酯咔唑生物碱(4)、7-羟基-3-甲酸甲酯咔唑生物碱(5)、2-羟基-3-醛基咔唑生物碱(6)、1-羟基-3-醛基咔唑生物碱(7)、2,3-二羟基-3-醛基咔唑生物碱(8)、3-醛基咔唑生物碱(9)、6-甲氧基-3-醛基咔唑生物碱(10)、7-甲氧基-3-甲酸甲酯咔唑生物碱(11)、2-甲氧基-3-羧基咔唑生物碱(12)、1,6-二羟基-3-醛基咔唑生物碱(13)。结论化合物9、10、12为首次从该植物中分离得到。化合物1、2、7、8、10对3种人体肿瘤细胞(A549、He La和BGC-823)均有不同程度的杀伤作用,IC50为8.53~19.87μg/m L。     

New carbazole alkaloids from Clausena anisata with antitumor promoting activity

Four new carbazole alkaloids, named clausamine D (1), E (2), F (3), and G (4), were isolated from Clausena anisata as inhibitors of Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells.     

Isolation, structure, and synthesis of novel 4-quinolinone alkaloids from Esenbeckia leiocarpa

Two new biocidal quinolinone alkaloids, 3-methoxy-1-methyl-2-propyl-4-quinolone [1] and 2(1'-ethylpropyl)-1-methyl-4-quinolone [2], were efficiently isolated using reversed-phase recycling hplc from the leaves of Esenbeckia leiocarpa. The structures were determined through spectroscopic data and confirmed by total synthesis. These alkaloids have antifeedant activities against the pink bollworm, Pectinophora gossypiella.     

Plant antimutagenic agents, 4. Isolation and structure elucidation of maesol, an inactive constituent of Maesa spp

Maesol, a novel dimeric phenol, was isolated from seeds of Maesa montana and Maesa indica. Maesol was shown to have the formula C28H42O4 with structure 1, a dimeric, symmetrical 1,12-bis(3,3'-dihydroxy-4,4'-dimethyl-5,5'-dimethoxyphenyl)dodecane. It is the first compound with such structure to be isolated from plant material. Structure elucidation was based largely on 1H- and 13C-nmr techniques and comparison with a known synthetic isomeric dimer 3. Although crude extracts showed strong inhibition of 2-aminoanthracene activity against Salmonella typhimurium (T-98), the pure compound was inactive when tested for inhibition of the mutagenic activity of several mutagens.     

Antineoplastic agents, 177. Isolation and structure of phyllanthostatin 6

The isolation and structural elucidation of a new Phyllanthus glycoside, phyllanthostatin 6 [7], was summarized. Phyllanthostatin 6 [7] was isolated from the roots of Phyllanthus acuminatus (Euphorbiaceae) and was found to inhibit (ED50 = 0.35 micrograms/ml) growth of the murine P-388 lymphocytic leukemia cell line. Two other new constituents were shown to be didesacetylphyllanthostatin 3 [9] and descinnamoylphyllanthocindiol [10]. Structure determinations were achieved employing hrfabms and 2D-nmr spectroscopy. Application of an hplc separation technique to the Phyllanthus glycosides and development of a new isolation procedure for the major antineoplastic constituent, phyllanthoside [1], are also described.     

Plant anticancer agents X. Isolation of camptothecin and 9-methoxycamptothecin from Ervatamia heyneana

The anticancer activity of the roots of Ervatamia heyneana (Apocynaceae) was found to be due principally to the known alkaloid, camptothecin (1). The closely related, but less active, 9-methoxycamptothecin (2) was also obtained. This is the first reported isolation of these biogenetically interesting alkaloids from the indole alkaloid rich Apocynaceae.     

Isolation of hypoglycemic phytoconstituent from Swietenia macrophylla seeds

The present study was undertaken to isolate a novel antidiabetic molecule from Swietenia macrophylla seeds. The hydroalcohol extract of Swietenia macrophylla seeds was subjected for bioassay guided isolation employing glucose utilization assay by the isolated rat hemi‐diaphragm method in vitro. One tetranortriterpenoid, swietenine, isolated from the chloroform fraction exhibited significant (p < 0.01) activity and the effect was comparable to that of human insulin (p < 0.01). Copyright © 2009 John Wiley & Sons, Ltd.