New erythrolides from the Caribbean gorgonian octocoral Erythropodium caribaeorum

Seven new briarane diterpenes, erythrolides K-Q (1-7), as well as the known compounds erythrolides A, B, C, F, and J have been isolated from samples of the Caribbean gorgonian Erythropodium caribaeorumcollected at Buccoo Reef and Flying Reef, Tobago. The structures of the new compounds were determined by high-resolution 1H and 13C NMR spectroscopy utilizing COSY, HMBC, HMQC, and NOESY experiments. The structures of erythrolides K and P were confirmed and their relative stereochemistry determined by X-ray crystallographic analysis.     

Phenguignardic acid and guignardic acid, phytotoxic secondary metabolites from Guignardia bidwellii

Bioactivity-guided isolation led to the identification of phenguignardic acid (2), a new phytotoxic secondary metabolite from submerged cultures of grape black rot fungus, Guignardia bidwellii. The compound is structurally related to guignardic acid (1), a dioxolanone moiety-containing metabolite isolated previously from Guignardia species. However, in contrast to guignardic acid, which is presumably synthesized from deamination products of valine and phenylalanine, the biochemical precursor for the biosynthesis of the new phytotoxin appears to be exclusively phenylalanine. Guignardic acid was also found in extracts of cultures from Guignardia bidwellii. The phytotoxic activities of both compounds were assessed in plant assays using either detached vine leaves or intact plants. Antimicrobial and cytotoxic activities of phenguignardic acid were determined.     

桂皮醛在大鼠肠中的体外代谢转化研究

目的 考察桂皮醛在大鼠离体小肠中的代谢转化特性及黄连对其代谢的影响.方法 RP-HPLC法测定桂皮醛及其代谢产物肉桂酸;考察不同浓度桂皮醛在大鼠离体小肠提取液、小肠组织匀浆液中的代谢动力学及黄连对其代谢的影响.结果 桂皮醛在各种大鼠离体小肠液中均可被迅速代谢,主要代谢产物为肉桂酸;小肠各提取液对桂皮醛的代谢速率存在差异;桂皮醛浓度越低,代谢速率越快;黄连对桂皮醛的大鼠小肠代谢存在明显抑制作用.结论 桂皮醛在大鼠小肠中可迅速被代谢,主要代谢产物为肉桂酸;黄连对桂皮醛代谢具有抑制作用.     

Glucosidation of betulinic acid by Cunninghamella species.

Microbial transformation of the antimelanoma agent betulinic acid (1) was studied. Preparative scale biotransformation with resting-cell suspensions of Cunninghamella species NRRL 5695 resulted in the production of a fungal metabolite of 1, which has been characterized as 28-O-beta-D-glucopyranosyl 3beta-hydroxy-lup-20(29)-en-28-oate (2) based on spectral and enzymic data. The in vitro cytotoxicity assay of metabolite 2 revealed no activity against several human melanoma cell lines.     

Marine natural products: pyrrololactams from several sponges

Two pyrrololactams, likely degradation products of more complex known guanidines, were isolated from several marine sponges. 5-Bromo- and 4,5-dibromopyrrole-1-carboxylic acid methyl esters were also isolated. A complex guanidine metabolite, poorly soluble in DMSO, was found to give sharp, reproducible nmr spectra in acid media.     

甘草酸和甘草次酸对芍药苷在大鼠体内药动学参数的影响

目的 研究甘草酸及其代谢产物甘草次酸对芍药中主要活性成分芍药苷在大鼠体内药动学特征的影响,探索芍药与甘草配伍用药的合理性.方法 大鼠单独ig给予芍药苷或分别与甘草酸、甘草次酸联合用药,于不同时间点采集血样,LC-MS测定芍药苷血药浓度,建立药物浓度-时间曲线,采用DAS2.1.1软件计算、分析药动学参数.结果 甘草酸能减小芍药苷Cmax、tmax,降低芍药苷AUC;甘草次酸能增加芍药苷Cma、tmax,显著提高芍药苷AUC.结论 甘草提高芍药苷生物利用度可能与甘草酸的代谢产物甘草次酸的作用相关.     

大鼠灌胃白花蛇舌草有效部位提取物血浆中代谢产物的液质分析

目的:分析大鼠灌胃白花蛇舌草有效部位提取物后血浆中对香豆酸、反式6-O-对香豆酰鸡屎藤苷甲酯及其代谢产物.方法:取健康雄性SD大鼠按0.4 g·kg-1的剂量经口给予白花蛇舌草有效部位提取物,1.0 h后采集眼眶静脉血液制备血浆,采用HPLC-Q-TOF-MS进行分析.结果:在大鼠血浆中只检测到1个代谢产物,并利用对照品鉴定了其结构为对香豆酸.结论:白花蛇舌草有效部位提取物中主要成分反式6-O-对香豆酰鸡屎藤苷甲酯在大鼠体内的代谢产物为对香豆酸,本实验为研究白花蛇舌草化学成分及药效作用提供了理论依据.     

Microbial transformations of the antimelanoma agent betulinic acid

Microbial transformation studies of the antimelanoma agent betulinic acid (1) were conducted. Screening experiments showed a number of microorganisms capable of biotransforming 1. Three of these cultures, Bacillus megaterium ATCC 14581, Cunninghamella elegans ATCC 9244, and Mucor mucedo UI-4605, were selected for preparative scale transformation. Bioconversion of 1 with resting-cell suspensions of phenobarbital-induced B. megaterium ATCC 14581 resulted in the production of the known betulonic acid (2) and two new metabolites: 3beta,7beta-dihydroxy-lup-20(29)-en-28-oic acid (3) and 3beta,6alpha, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (4). Biotransformation of 1 with growing cultures of C. elegans ATCC 9244 produced one new metabolite characterized as 1beta,3beta, 7beta-trihydroxy-lup-20(29)-en-28-oic acid (5). Incubation of 1 with growing cultures of M. mucedo UI-4605 afforded metabolite 3. Structure elucidation of all metabolites was based on NMR and HRMS analyses. In addition, the antimelanoma activity of metabolites 2-5 was evaluated against two human melanoma cell lines, Mel-1 (lymph node) and Mel-2 (pleural fluid).     

Bastadin 21, a novel isobastarane metabolite from the Great Barrier Reef marine sponge Ianthella quadrangulata

Bastadin 21, a novel tribrominated bastadin with the uncommon isobastarane skeleton, was isolated from the Great Barrier Reef marine sponge Ianthella quadrangulata. The structure was elucidated on the basis of the 1D and 2D NMR and MS data of bastadin 21 and its tetramethyl ether.     

Kalanchosine dimalate, an anti-inflammatory salt from Kalanchoe brasiliensis

This report describes the isolation and characterization of kalanchosine dimalate (KMC), an anti-inflammatory salt from the fresh juice of the aerial parts of Kalanchoe brasiliensis. KMC comprises the new metabolite kalanchosine (1) and malic acid (2) in a 1:2 stoichiometric ratio. Kalanchosine (1), 3,6-diamino-4,5-dihydroxyoctanedioic acid, is the first naturally occurring dimeric bis(gamma-hydroxy-beta-amino acid) and is at least partially responsible for the anti-inflammatory properties of K. brasiliensis.