奶子藤属植物中生物碱研究进展

奶子藤属植物为傣族传统常用药材,含有大量结构复杂,生物活性良好的生物碱类成分。本文针对奶子藤属植物中已分离鉴定的95个生物碱及其体外抗肿瘤和抗HIV活性研究进行了系统综述,为更加合理地开发利用奶子藤属植物资源提供参考依据。     

Five new alkaloids from Aconitum apetalum (Ranunculaceae)

Twenty-one alkaloids, including five new ones, acoapetaldines A–E (1–5), were isolated from the whole plants of Aconitum apetalum. Among them, 1 is an aconitine-type diterpenoid alkaloid, 2 and 3 are aporphine alkaloids and 4 and 5 are napelline-type diterpenoid alkaloids. The structures of the new alkaloids were elucidated by spectroscopic data analysis and that of acoapetaldine D (4) was confirmed by single crystal X-ray crystallography. Acoapetaldine A (1) and aconorine (12) exhibited moderate anti-tobacco mosaic virus (anti-TMV) activity, while corydine (15) displayed moderate antimicrobial activity against Pseudomonas aeruginosa.     

Merremiadissecta (Convolvulaceae): Condiment, medicine, ornamental, and weed—a review

Merremia dissecta was first discovered in the Caribbean, then Florida, Mexico, and later in the Old World, where it had been introduced. Historically and currently, the species has been used as a condiment, medicine, and ornamental by an array of cultures. Although the plant has escaped in several areas to become a weed, it continues being sold as an ornament in even those regions. In Argentina, roots ofM. dissecta var. edentata are still used as food by a few indigenous groups. History, uses, and chemistry are discussed regarding these utilizations.

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Merremia dissecta (Convolvulaceas): Un condimento, medicina, ornamental, y maleza— Una revista

Resumen  Merremia dissecta fue primeramente descubierta en el Caribe, luego en la Florida, México y más tarde fue introducida en el Viejo Mundo. Históricamente y aún actualmente se ha usado como condimento, medicina, y ornamentatión por varias culturas. A pesar de que en varias áreas se ha transformado en una mala hierba, se continua vendiendo como un ornamento aún en esas areas. En Argentina, as raices deM. dissecta var. edentata aún son usadas como alimento por unos cuantos grupos indígenas. La historia, los usos y la química de estas utilizaciónes son aquí discutidas.

     

Secophnane-type alkaloids from Daphniphyllum oldhami

Four new alkaloids, daphnioldhanins D-G (1-4, resp.), together with five known alkaloids, daphmacropodine (5), secodaphniphylline (6), deoxycalyciphylline B (7), deoxyisocalyciphylline B (8), and daphmanidin A (9), were isolated from the roots of Daphniphyllum oldhami. Their structures were elucidated on the basis of spectroscopic data and chemical methods. Compound 1 at 2.0 microM showed potent antioxidant activity against H(2)O(2)-induced impairment in PC12 cells.     

Glucosides from the roots of Capparis tenera

Two new lignan glucosides, compounds 2 and 3, two new 1H-indole-alkaloid glucosides, 5 and 6, as well as two new phenolic glucosides, 7 and 10, were isolated from the roots of Capparis tenera, together with five known compounds. Their structures were characterized by chemical and spectroscopic methods. Most of these isolates were obtained for the first time from Capparidaceae. The antioxidant and anti-inflammatory activities of the new compounds were investigated.     

Overproduction of medicinal ergot alkaloids based on a fungal platform

Privileged ergot alkaloids (EAs) produced by the fungal genus Claviceps are used to treat a wide range of diseases. However, their use and research have been hampered by the challenging genetic engineering of Claviceps. Here we systematically refactored and rationally engineered the EA biosynthetic pathway in heterologous host Aspergillus nidulans by using a Fungal-Yeast-Shuttle-Vector protocol. The obtained strains allowed the production of diverse EAs and related intermediates, including prechanoclavine (PCC, 333.8 mg/L), chanoclavine (CC, 241.0 mg/L), agroclavine (AC, 78.7 mg/L), and festuclavine (FC, 99.2 mg/L), etc. This fungal platform also enabled the access to the methyl-oxidized EAs (MOEAs), including elymoclavine (EC), lysergic acid (LA), dihydroelysergol (DHLG), and dihydrolysergic acid (DHLA), by overexpressing a P450 enzyme CloA. Furthermore, by optimizing the P450 electron transfer (ET) pathway and using multi-copy of cloA, the titers of EC and DHLG have been improved by 17.3- and 9.4-fold, respectively. Beyond our demonstration of A. nidulans as a robust platform for EA overproduction, our study offers a proof of concept for engineering the eukaryotic P450s-contained biosynthetic pathways in a filamentous fungal host.     

Engineering tropane alkaloid production and glyphosate resistance by overexpressing AbCaM1 and G2-EPSPS in Atropa belladonna

Atropa belladonna is an important industrial crop for producing anticholinergic tropane alkaloids (TAs). Using glyphosate as selection pressure, transgenic homozygous plants of A. belladonna are generated, in which a novel calmodulin gene (AbCaM1) and a reported EPSPS gene (G2-EPSPS) are co-overexpressed. AbCaM1 is highly expressed in secondary roots of A. belladonna and has calcium-binding activity. Three transgenic homozygous lines were generated and their glyphosate tolerance and TAs’ production were evaluated in the field. Transgenic homozygous lines produced TAs at much higher levels than wild-type plants. In the leaves of T2GC02, T2GC05, and T2GC06, the hyoscyamine content was 8.95-, 10.61-, and 9.96 mg/g DW, the scopolamine content was 1.34-, 1.50- and 0.86 mg/g DW, respectively. Wild-type plants of A. belladonna produced hyoscyamine and scopolamine respectively at the levels of 2.45 mg/g DW and 0.30 mg/g DW in leaves. Gene expression analysis indicated that AbCaM1 significantly up-regulated seven key TA biosynthesis genes. Transgenic homozygous lines could tolerate a commercial recommended dose of glyphosate in the field. In summary, new varieties of A. belladonna not only produce pharmaceutical TAs at high levels but tolerate glyphosate, facilitating industrial production of TAs and weed management at a much lower cost.     

Anti-inflammatory and antiproliferative prenylated carbazole alkaloids from Clausena vestita

Twelve prenylated carbazole alkaloids, containing a novel prenylated carbazole alkaloid, named as clausevestine (1), and 11 known prenylated carbazole alkaloids (2–12), were isolated and identified from the stems and leaves of Clausena vestita, which is a Chinese endemic plant. The chemical structure of 1 was established by means of comprehensive spectroscopic data analyses and the known compounds were determined via comparing their NMR and MS data as well as optical rotation values with those reported in literature. Especially, clausevestine (1) is an unusual prenylated carbazole alkaloid possessing an unprecedented carbon skeleton holding 20 carbon atoms. The anti-inflammatory effects and antiproliferative activities of those isolated prenylated carbazole alkaloids were tested. Prenylated carbazole alkaloids 1–12 displayed remarkable inhibitory effects on NO (nitric oxide) production with IC₅₀ values equivalent to that of the positive control (hydrocortisone). Meanwhile, prenylated carbazole alkaloids 1–12 exhibited remarkable antiproliferative activities against diverse human cancer cell lines in vitro holding the IC₅₀ values ranging from 0.32 ± 0.04 to 18.76 ± 0.18 µM. These findings indicate that these prenylated carbazole alkaloids possessing remarkable anti-inflammatory effects and antiproliferative activities could be meaningful to the discovery of new anti-inflammatory and anti-tumor candidate drugs.     

Bioactive monoterpene indole alkaloids from Nauclea officinalis

Two new monoterpene indole alkaloids, naucleaoffines A (1) and B (2), together with six known alkaloids (3–8), were isolated from the stems and leaves of Nauclea officinalis. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with the data reported in literature. All isolated compounds were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–8 exhibited significant inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC₅₀ values comparable to that of hydrocortisone. In addition, compounds 1–8 showed significant anti-HIV-1 activities with EC₅₀ ranged from 0.06 to 2.08 µM. These findings suggest that the discoveries of these indole alkaloids with significant anti-inflammatory activities and anti-HIV-1 activities isolated from N. officinalis could be of great importance to the development of new anti-inflammatory and anti-HIV agents.     

Phytochemical investigation of Eremostachys moluccelloides Bunge (Lamiaceae)

Phytochemical investigation of the aerial parts of Eremostachys moluccelloides Bunge led to the identification of a new diterpene, 2β,14-dihydroxy −11-formyl- 12-carboxy-13-des-isopropyl-13-hydroxymethyl-abieta-8,11,13- triene- 16(17)- lactone (1), along with the known compounds 12, 18-dicarboxy-14-hydroxy-13-des -isopropyl-13-hydroxymethyl- abieta-8,11,13-triene-16(17)-lactone (2), 5-hydroxy-3′,4′,7-trimethoxyflavone (3), 5-hydroxy-4’,7-dimethoxyflavone (4), luteolin-7-O-β-glucoside (5), verbascoside (6), luteolin 7-O-(6″-O-β-D-apiofuranosyl) -β-D-glucopyranoside (7), chlorogenic acid (8), echinacoside (9), apigenin-7-O-β-D-glucoside (10), p-coumaric acid (11), vanillic acid (12), apigenin-7-O-(6″-E-p-coumaroyl)-β-D-glucopyranoside (13), apigenin-7-O-(3″,6″-E-p-dicoumaroyl)-β-glucoside (14), lamalbide (15), 6β-hydroxy-7-epi-loganin (16), phloyoside II (17) The structures were elucidated on the basis of 1D and 2D NMR spectroscopy, UV, MS and by comparison with compounds previously reported in the literature. Compounds 1–4, 8, 9, 11, 12, 14 have not been reported previously from any species within the genus Eremostachys. Compounds 1–14, 17 were obtained from this species for the first time. The chemotaxonomic significance of the isolated compounds is discussed.