海洋天然产物喹啉类生物碱的生物活性研究进展

海洋天然产物喹啉类生物碱是从海洋生物中提取的次级代谢产物,具有新颖的化学结构和广谱的生物活性,是多种新药开发研制的先导化合物.对海洋天然产物喹啉类生物碱的来源及生物活性进行了综述,并对其发展前景进行了展望.     

苄基异喹啉类生物碱的药理活性研究进展

苄基异喹啉类生物碱(Benzylisoquinoline alkaloids,BA)药理活性广泛,药理学研究已经证实苄基异喹啉类生物碱具有抗肿瘤、抗炎、抗氧化、心血管保护、抗菌、肌肉松弛以及中枢神经系统等方面的药理作用。另外,抗埃博拉病毒等新活性的发现也为苄基异喹啉类生物碱的进一步研究注入新的活力。本文通过总结近十年国内外的相关文献,对BA的药理活性进行了综述。     

综述异喹啉类生物碱分离与分析研究进展

异喹啉类生物碱是一类生物活性非常强的化学物质,具较强的药用价值。综述了异喹啉类化合物的提取原理及技术的研究进展,同时介绍了该类化合物检测技术的原理及方法。     

杂环类植物抗病毒剂的研究进展

介绍了近年来杂环类植物抗病毒剂的研究进展及开发情况，杂环类植物抗病毒剂化合物主要包括生物碱，吡啶衍生物，吡唑衍生物，咪唑衍一物，三唑衍生物，四唑衍生物，噻唑衍生物，噻二唑衍生物，吡唑衍生物，三嗪衍生物及喹啉肟醚等十一类。     

异喹啉类生物碱和G-四链体结合的分子动力学研究

G-四链体是核酸的一种非经典二级结构,主要出现于富含鸟嘌呤（G）碱基的DNA或RNA序列。生物体内的G-四链体主要形成于端粒区域和某些原癌基因的启动子区域,是生物医学研究的重要对象。以G-四链体作为靶点的抗癌策略虽被多次提出,但目前还未有成功进入临床试验的案例。因此,有关原癌基因启动子区域的G-四链体与配体结合的研究,可以对靶向抗癌药物的设计提供指导性建议。使用分子动力学模拟的方法,研究了不同的异喹啉类生物碱与G-四链体的结合机理。通过考察四种异喹啉配体与G-四链体结合的过程,得到了异喹啉配体与G-四链体稳定结合的构象以及结合的主导因素。此工作从原子分子层面深化了对异喹啉类生物碱和G-四链体结合机理的微观认识,对抗癌药物设计具有指导意义。     

化妆品中生物碱类风险物质的安全监测

围绕化妆品中生物碱类风险物质的安全性、我国关于化妆品中生物碱类风险物质的管理规定和检测方法以及国外对于生物碱类风险物质的规定等进行阐述,提出关于加强化妆品中生物碱类风险物质风险监管的建议和措施。     

乌头类药材中的生物碱质谱检测技术的研究进展

乌头类中药是一种兼具"毒效双性"中药,具有回阳救逆、祛风除湿、消炎止痛等功效,但服用过量易中毒,甚至死亡,每年服用乌头类中药中毒死亡的案例屡见不鲜。乌头生物碱分析方法对于医学诊断及刑侦方面具有重要作用。因此,本文简述了乌头类生物碱的毒理作用,综述了乌头类药材中的生物碱不同的质谱技术,比较了不同检测技术的优缺点,并对乌头类生物碱的质谱检测技术进行了总结和展望。     

莲心碱提取分离的研究进展

莲心碱是莲子心中一种主要的双苄基异喹啉类生物碱,具有抗心律失常、降压等心血管系统活性。概述了莲心碱的性质、结构鉴定方法,介绍了莲心碱检测及提取分离方法的研究进展情况。     

农药用生物碱的研究进展

综述了杀虫生物碱、灭鼠生物碱及灭菌生物碱的最新研究进展。苦参碱和烟碱在我国已进人工业化开发。黎芦碱、小蘖碱、雷公藤生物碱、甾醇生物碱均显示出良好的杀虫活性，番木鳖碱可用于灭鼠。而吡咯里西啶类生物碱则具有较强的杀菌活性。     

龙葵甾体类生物碱的表征及其在该植物体内的形成、变化

用醇提-酸醇水解法提取了龙葵内的澳洲茄胺,对其进行了定性、定量分析;以澳洲茄胺为参照品,表征了甾体类生物碱在龙葵中所占质量分数,考察了龙葵果实成长期内甾体类生物碱的形成、变化趋势。发现甾体类生物碱主要富集在龙葵未成熟果实中,检测出其在未成熟果实内的质量分数最高达到3.52%;茎叶所含甾体类生物碱的质量分数低于0.5%。果实内甾体类生物碱的变化在其生长中经历了增加、减少两个时段,在结果一个月后,果实内的甾体类生物碱质量分数达到最大,高达2.5%以上;果实成熟时甾体类生物碱质量分数反而最小,低于1%;阳光照射程度的不同会改变龙葵果实的生长期,从而对甾体类生物碱的质量分数变化产生影响。因此,龙葵的采摘及其生物碱入药,需着重考虑生物碱在该植物不同部位的分布及生长周期、阳光照射等因素。     

Detrimental effects ofCinchona leaf alkaloids on larvae of the polyphagous insectSpodoptera exigua

YoungCinchona ledgeriana plants contain two types of alkaloid: indole alkaloids in the leaves and quinoline alkaloids in the root. FromCinchona leaves, a crude alkaloid extract was made, containing the cinchophylline type of indole alkaloids and a small amount of 5-methoxytryptamine. The leaf alkaloid extract exerted a strong detrimental effect on the growth of larvae of the polyphagous beet armyworm,Spodoptera exigua (Lepidoptera). Feeding of larvae on an artificial diet containing the leaf alkaloids at the same concentrations as those found in the plant resulted in significant growth reduction, retardation in development, and mortality of the larvae. Cinchophyllines are composed of 5-methoxytryptamine coupled to a corynantheal unit. When incorporated into the artificial diet, 5-methoxytryptamine alone had no effect on the 5.exigua larvae. Corynantheal, however, had a strong detrimental effect on growth of the larvae, its effect being comparable to that of the leaf alkaloid extract. In contrast to the indole-type leaf alkaloids, the quinolinetypeCinchona root alkaloids did not affect growth and development of the larvae. These results suggest that the indole-type alkaloids, which inCinchona plants are present at the highest concentrations in the young, vulnerable leaflets, are involved in the chemical defense of the plant against herbivorous insects.     

Identification of the cytochrome P450 monooxygenase that bridges the clavine and ergoline alkaloid pathways

Clavines and D-lysergic acid-derived alkaloid amides and alkaloid peptides are two different families of compounds that have the indole-derived tetracyclic metergoline ring system in common. Previous work has shown that D-lysergic acid is biosynthetically derived from clavine alkaloids. Recent cloning and analysis of the ergot alkaloid biosynthesis gene cluster from the D-lysergic acid peptide (ergopeptines)-producing Claviceps purpurea, has shown that it most probably contains all genes necessary for D-lysergic acid synthesis as well as those that encode the assembly of D-lysergic acid peptides, such as ergotamine. To address the role of the oxygenase genes of alkaloid-gene clusters, the only cytochrome P450 monooxygenase gene of this cluster was inactivated by disruption. The resultant mutant accumulated agroclavine, elymoclavine, and chanoclavine in substantial amounts but not ergopeptines. Feeding the mutant with D-lysergic acid restored ergopeptine synthesis; this suggests a block in the conversion of elymoclavine to D-lysergic acid. The gene was designated cloA (for encoding a clavine oxidase, CLOA). Retransformation of the mutant with the intact cloA gene also restored ergopeptine synthesis. These data show that CLOA catalyses the conversion of clavines to D-lysergic acid, it acts as a critical enzyme in the ergot alkaloid gene cluster, and bridges the biosynthesis of the two different families of alkaloids.     

Pyrrolizidine alkaloid content in crude and processed borage oil from different processing stages

The pyrrolizidine alkaloid content of crude borage oil and borage oil from different processing stages was determined by GC-MS. The results showed that no pyrrolizidine alkaloids were present above a detection limit of 20 ppb. The reduction factors for pyrrolizidine alkaloids at various stages in the oil refining process were determined by means of spiking experiments using the commercially available pyrrolizidine alkaloid crotaline. It was shown that the pyrrolizidine content in crude borage oil was reduced overall by a factor of about 30,000 in the refining process.     

牛心朴子草中生物碱的抑制植物病毒活性研究

牛心朴子草广泛分布于我国西北旱沙荒漠地带,笔者发现其提取物中生物碱部位对危害极大的烟草花叶病毒(TMV)具有很高的抑制活性。生物活性跟踪与色谱分离、结构鉴定确认该生物碱属于菲并吲哚里西啶,活性成份为安托芬(1)和6-羟基-2,3-二甲氧基菲并吲哚里西啶(2)。此外,还分离得到另外三种生物碱。构效关系表明氮上孤电子对和菲环对高的抗病毒活性是必要的。     

不同产地马齿苋总生物碱的含量测定

通过连续回流法对马齿苋进行提取,经过滤、萃取、洗涤、萃取等提纯,得马齿苋总生物碱精制品,以咖啡因为标准品对马齿苋总生物碱进行紫外含量测。结果表明,在浓度0.05~0.30 mg/m L范围内线性良好,r=0.999 35;平均加样回收率为(98.1±2.4)%;不同产地马齿苋总生物碱含量具有明显的差别,贵州0.090%,四川0.066%,北京0.082%,西安0.059%,马齿苋总生物碱含量贵州北京四川西安。     

Absolute Configuration of the Indole Alkaloid (-)-Mehranine Hydrobromide

The structure including the absolute configuration of the indole alkaloid (-)-mehranine hydrobromide (1·HBr) has been assigned by X-ray analysis. This result gave the possibility to assign the absolute configurations of some related alkaloids     

A Functional Explanation for Patterns of Norditerpenoid Alkaloid Levels in Tall Larkspur (Delphinium barbeyi)

Concentrations of norditerpenoid alkaloids vary among larkspur (Delphinium) species, locations, and years, but environmental stresses seem to have little effect on alkaloid levels. There is a need for a functional hypothesis of alkaloid synthesis and metabolism to explain the observed trends in concentration and to predict the toxicity of larkspur populations. This study was replicated at two locations over two years in the mountains of central Utah. Ten tall larkspur (D. barbeyi) plants were marked at each location, and a single stalk was harvested from each plant at weekly intervals throughout the growing season. Concentrations of toxic and total alkaloids were measured by Fourier-transformed infrared spectroscopy (FTIR), and alkaloid pools were calculated by multiplying the alkaloid concentration by the dry weight of the plant to determine the amount of alkaloids in the stalk. Alkaloid pools in the stalks increased for the first three weeks, leveled off, and then declined to low levels as the plants began to senesce. Concentrations of alkaloids declined through the season, as the alkaloids were diluted in the increasing biomass as the plants grew. These patterns will be used to predict potential toxicity of larkspur populations.     

Short-term induction of alkaloid production in lupines Differences between N2-fixing and nitrogen-limited plants

We used N₂-fixing and nonfixing lupines to examine the effects of plant nutrition on short-term alkaloid production in damaged leaves. Three different treatments were used: damaged leaves from N₂-fixing plants; undamaged leaves from these damaged, N₂-fixing plants; and damaged leaves on nitrogen-limited, nonfixing plants. Relative to controls, alkaloids increased in concentration more quickly in the N₂-fixing than in the nitrogen-limited plants. The magnitude of this increase in alkaloids was correlated with the initial alkaloid concentration. These results suggest that nitrogen-rich plants may benefit from faster and higher alkaloid induction than nitrogen-limited plants. In addition, the detailed dynamics of individual alkaloids are consistent with earlier proposals for the mechanism of lupine alkaloid induction.     

Influence of alkaloid concentration on acceptability of tall larkspur (Delphinium spp.) to cattle and sheep

Tall larkspur (Delphinium spp.) is a serious toxic plant problem on western U.S. ranges. The major toxins in tall larkspur are methyllycaconitine (MLA) and 14-deacetylnudicauline (14-DAN); the sum of both is termed the toxic alkaloid concentration. Toxic alkaloids comprise about 20–50% of the total alkaloid concentration in tall larkspur. Toxic and total alkaloid concentration generally declines with maturity, whereas cattle and sheep consumption of larkspur typically increases with plant maturity. We hypothesized that cattle and sheep consumption of tall larkspur was negatively related to higher concentrations of total or toxic alkaloid. We compared consumption of several collections of dried, ground larkspur and fresh larkspur in a series of trials. In another trial, a crude alkaloid fraction was extracted with ethanol, added to alfalfa hay, and consumption compared to untreated alfalfa hay, alcohol-treated hay, and the essentially alkaloid-free plant residue. In all cases we correlated amounts eaten with total and toxic alkaloid concentration. A grazing trial was also conducted to relate larkspur consumption over time to alkaloid concentrations. Total alkaloid concentrations in dried, whole-plant collections ranged from 9.3 to 38.8 mg/g of dry weight, whereas toxic alkaloid concentrations varied from 0.0 to 7.1 mg/g. In one pen trial, cattle preferred a larkspur collection (P<0.01) that contained no toxic alkaloids but had a high total alkaloid concentration (39 mg/g). There was no correlation (P>0.05), however, between concentrations of total or toxic alkaloids and amount of dry plant consumed in this or any other trial. Conversely, sheep consumption tended to be negatively influenced by total and toxic alkaloid concentration (P0.08). In the trials with extract, cattle preferred the alcohol-treated hay and rejected the alkaloid-free residue (P<0.01), whereas the alkaloid-treated hay was of intermediate acceptability. Cattle preferred the alkaloid-treated hay over the alkaloid-free residue, indicating that alkaloids did not deter consumption. Conversely, the alkaloid-treated hay was less preferred than either untreated or alcohol-treated hay, suggesting a negative effect on acceptability. There was no correlation between alkaloid concentration and amount of treated feed eaten. In field trials, the amount of composited, fresh leaves or flowers eaten by cattle was influenced by plant part (P=0.04), but was not related (P>0.05) to alkaloid concentration. Cattle preferred leaves over flowers when offered individual plants differing in phenological stage and/or amount of shade, but alkaloid concentration was not related to consumption. We conclude that knowledge of the concentration of total or toxic alkaloid in tall larkspur will give little or no indication of plant acceptability to cattle. Even though accurate predictions can be made about the potential toxicity of larkspur based on the concentration of toxic alkaloids, predictions about consumption must be based primarily on plant phenology.     

Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid

Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches.