New skeletons and new concepts in Amaryllidaceae alkaloids

The Amaryllidaceae alkaloids, represent a group of isoquinoline alkaloids, which are produced almost solely by members of the Amaryllidaceae family. The alkaloids of this family have attracted considerable amount of interest due to some important pharmacological activities they were shown to possess. In the last decade, our phytochemical studies on four Galanthus (Amaryllidaceae) species of Turkish origin have yielded quite a number of new alkaloids with diverse structures. Among these alkaloids, gracilines and plicamines constitute two new subgroups for the Amaryllidaceae alkaloids. The gracilines contain an incorporated 10b,4a-ethanoiminodibenzo[b,d]pyrane skeleton. The plicamines are dinitrogenous compounds, where the oxygen atom in position 7 of a tazettine skeleton is replaced by a nitrogen atom substituted by a pendant 4-hydroxyphenethyl moiety. One of the new alkaloids, galanthindole, which possesses a nonfused indole ring, unlike the already known subgroups of Amaryllidaceae alkaloids, may be considered as the prototype of a third new subgroup of the Amaryllidaceae alkaloids. Additionally, two known isoquinoline alkaloids which do not possess one of the established skeletons of the Amaryllidaceae alkaloids, namely ( − )-capnoidine and (+)-bulbocapnine, have been isolated from a Turkish Galanthus species. Totally, 21 new, 20 known alkaloids and 2 known lignans have been characterized. In this review, the isolation and structure elucidation of these compounds with interesting chemical structures are described.     

Cellular distribution of alkaloids and their translocation via phloem and xylem: the importance of compartment pH

The physico‐chemical background of alkaloid allocation within plants is outlined and discussed exemplarily for pyrrolizidine alkaloids (PAs) and nicotine. The trigger for this discourse is the finding that, for example, PAs, which are taken up from the soil, are translocated in the xylem, whereas – when genuinely present in plants – they are allocated as N‐oxides via phloem. Special emphasis is put on the impact of different pH values in certain compartments, as this entails significant changes in the relative lipophilic character of alkaloids: tertiary alkaloids diffuse readily through biomembranes, while the corresponding protonated alkaloids are retained in acidic compartments, i.e. vacuoles or xylem. Therefore, this phenomenon, well known as the ‘ion trap mechanism’, is also relevant for long‐distance transport of alkaloids. Any efficient allocation of typical tertiary alkaloids within the phloem can thus be excluded. In contrast, due to their strongly increased hydrophilic properties, alkaloid‐N‐oxides or quarternary alkaloids cannot diffuse through biomembranes and, consequently, would be retained in the acidic xylem during translocation. The major aim of this paper is to sharpen the mind for the chemical peculiarities of alkaloids and to consider them adequately in forthcoming investigations on allocation of alkaloids.     

Alkaloid evolution and angiosperm systematics

The correlation of biosynthetic steps leading to the primary precursors of the shikimate pathway with the distribution of derived alkaloids on dahlgren's system of classification of angiosperm orders suggests that evolution paralleled gradual blocking of these steps. Phenylalanine-derived alkaloids, with the centre of radiation situated in the magnoliales, are of widespread occurrence in angiosperms, an indication of the antiquity of the character. Anthranilic acid-derived alkaloids, with the centre of radiotion in the rutales, are less widespread. Orders in which such alkaloids co-occur with the former biogenetic group are considered to be of more recent origin. Finally, mevalonate-derived iridoid alkaloids, with the centre of radiation in the gentianales, are even less widespread. Orders in which such alkaloids co-occur with the former biogenetic groups should thus be of still more recent origin. These concepts are summarized bg a phylogenetic tree, which illustrates the divergence of three major groups of angiosperm superorders.     

Bromo- and Iodo-Containing Alkaloids from Marine Microorganisms and Sponges

The taxonomic distribution, structure, and biological activity of halogenated alkaloids isolated from marine microorganisms and sponges are reviewed. The structures of nearly 140 natural bromo- and iodo-containing alkaloids are shown.     

Turnover and transport of quinolizidine alkaloids. Diurnal fluctuations of lupanine in the phloem sap,leaves and fruits of Lupinus albus L.

Quinolizidine alkaloids formed in the leaves of Lupinus albus L. are translocated via the phloem to the other plant organs, especially the maturing fruits. Compared with amino-acid transport in the phloem, the alkaloids contribute about 8% to the overall nitrogen being exported from the leaf. Since it is likely that the alkaloids are subsequently degraded in the target tissues a minor role of quinolizidine alkaloids might be nitrogen transport. A marked diurnal fluctuation of alkaloids was observed in the leaves, the phloem sap, the roots and the fruits with an increase during the day and an amplitude of several hundred percent thus providing evidence for a rapid turnover of endogenous alkaloids.Abbreviations QA quinolizidine alkaloids - GLC gas-liquid chromatography     

Rapid selective screening and determination of ephedrine alkaloids using GC-MS footnote mark

Ephedra (ma huang) has been widely used as an herb or herbal extract in both traditional Chinese medicine and Western world dietary supplements. The effects of Ephedra have been attributed to a series of six ephedrine alkaloids including ephedrine and pseudoephedrine. A GC-MS method for the ephedrine alkaloids is described which couples ammoniacal chloroform as the extraction solvent with a two-stage derivatisation scheme. This scheme produces the O-trimethylsilyl, N-trifluoracetyl derivatives (O-TMS, N-TFA) for the primary and secondary amine alkaloids, and the O-TMS derivatives for the tertiary amine alkaloids. Relatively clean extracts are obtained from complex matrices, and the six ephedrine alkaloids are effectively separated and identified. This approach was also evaluated for quantitative analysis, and was shown to provide quantitative results for ephedrine and pseudoephedrine, and good estimates for the four minor alkaloids. Figures of merit are presented for linearity, detection limits, precision and accuracy. We have applied this approach to the rapid screening and profiling of the ephedrine alkaloids in whole Ephedra plants, liquid plant extracts, dried powder plant extracts and a variety of Ephedra-containing dietary supplements.     

Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domesticated silkworms: enzymatic adaptation of Bombyx mori to mulberry defense

Mulberry leaves (Morus spp.) exude latex rich in sugar-mimic alkaloids, 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1) and 1-deoxynojirimycin (DNJ), as a defense against herbivorous insects. Sugar-mimic alkaloids are inhibitors of sugar-metabolizing enzymes, and are toxic to the Eri silkworm, Samia ricini, a generalist herbivore, but not at all to the domesticated silkworm, Bombyx mori, a mulberry specialist. To address the phenomena, we fed both larvae diets containing different sugar sources (sucrose, glucose or none) with or without sugar-mimic alkaloids from mulberry latex. In S. ricini, addition of sugar-mimic alkaloids to the sucrose (the major sugar in mulberry leaves) diet reduced both growth and the absorption ratio of sugar, but it reduced neither in B. mori. The midgut soluble sucrase activity of S. ricini was low and inhibited by very low concentrations of sugar-mimic alkaloids (IC₅₀=0.9–8.2 μM), but that of B. mori was high and not inhibited even by very high concentrations (IC₅₀>1000 μM) of sugar-mimic alkaloids. In S. ricini, the addition of sugar-mimic alkaloids to the glucose diet still had considerable negative effects on growth, although it did not reduce the absorption ratio of glucose. The hemolymph of S. ricini fed sugar-mimic alkaloids contained sugar-mimic alkaloids. The trehalose concentration in the hemolymph increased significantly in S. ricini fed sugar-mimic alkaloids, but not in B. mori. The trehalase activities of S. ricini were lower and inhibited by lower concentrations of sugar-mimic alkaloids than those of B. mori. These results suggest that sugar-mimic alkaloids in mulberry latex exert toxicity to S. ricini larvae first by inhibiting midgut sucrase and digestion of sucrose, and secondly, after being absorbed into hemolymph, by inhibiting trehalase and utilization of trehalose, the major blood sugar. Further, our results reveal that B. mori larvae evolved enzymatic adaptation to mulberry defense by developing sucrase and trehalase that are insensitive to sugar-mimic alkaloids.     

Biodiversity of Convolvulaceous species that contain ergot alkaloids,indole diterpene alkaloids,and swainsonine

Convolvulaceous species have been reported to contain several bioactive principles thought to be toxic to livestock including the calystegines, swainsonine, ergot alkaloids, and indole diterpene alkaloids. Swainsonine, ergot alkaloids, and indole diterpene alkaloids are produced by seed transmitted fungal symbionts associated with their respective plant host, while the calystegines are produced by the plant. To date, Ipomoea asarifolia and Ipomoea muelleri represent the only Ipomoea species and members of the Convolvulaceae known to contain indole diterpene alkaloids, however several other Convolvulaceous species are reported to contain ergot alkaloids. To further explore the biodiversity of species that may contain indole diterpenes, we analyzed several Convolvulaceous species (n = 30) for indole diterpene alkaloids, representing four genera, Argyreia, Ipomoea, Stictocardia, and Turbina, that had been previously reported to contain ergot alkaloids. These species were also verified to contain ergot alkaloids and subsequently analyzed for swainsonine. Ergot alkaloids were detected in 18 species representing all four genera screened, indole diterpenes were detected in two Argyreia species and eight Ipomoea species of the 18 that contained ergot alkaloids, and swainsonine was detected in two Ipomoea species. The data suggest a strong association exists between the relationship of the Periglandula species associated with each host and the occurrence of the ergot alkaloids and/or the indole diterpenes reported here. Likewise there appears to be an association between the occurrence of the respective bioactive principle and the genetic relatedness of the respective host plant species.     

异甾体生物碱类化合物及药理活性研究进展

异甾体生物碱类结构多变,药理活性多样,主要分布于百合科贝母属和藜芦属植物中。近十五年内共报道了80个新发现的异甾体生物碱类成分,药理活性涉及抗炎、镇痛、降压、平喘、抗血栓、胆碱酯酶抑制、抗病毒和抗肿瘤等作用。本文综述了2006至2020年间该类化合物的植物来源、化学结构及药理活性,并对该类化合物的未来研究探索进行了讨论与展望。     

Acquisition, transformation and maintenance of plant pyrrolizidine alkaloids by the polyphagous arctiid Grammia geneura

The polyphagous arctiid Grammia geneura appears well adapted to utilize for its protection plant pyrrolizidine alkaloids of almost all known structural types. Plant-acquired alkaloids that are maintained through all life-stages include various classes of macrocyclic diesters (typically occurring in the Asteraceae tribe Senecioneae and Fabaceae), macrocyclic triesters (Apocynaceae) and open-chain esters of the lycopsamine type (Asteraceae tribe Eupatorieae, Boraginaceae and Apocynaceae). As in other arctiids, all sequestered and processed pyrrolizidine alkaloids are maintained as non-toxic N-oxides. The only type of pyrrolizidine alkaloids that is neither sequestered nor metabolized are the pro-toxic otonecine-derivatives, e.g. the senecionine analog senkirkine that cannot be detoxified by N-oxidation. In its sequestration behavior, G. geneura resembles the previously studied highly polyphagous Estigmene acrea. Both arctiids are adapted to exploit pyrrolizidine alkaloid-containing plants as "drug sources". However, unlike E. acrea, G. geneura is not known to synthesize the pyrrolizidine-derived male courtship pheromone, hydroxydanaidal, and differs distinctly in its metabolic processing of the plant-acquired alkaloids. Necine bases obtained from plant acquired pyrrolizidine alkaloids are re-esterified yielding two distinct classes of insect-specific ester alkaloids, the creatonotines, also present in E. acrea, and the callimorphines, missing in E. acrea. The creatonotines are preferentially found in pupae; in adults they are largely replaced by the callimorphines. Before eclosion the creatonotines are apparently converted into the callimorphines by trans-esterification. Open-chain ester alkaloids such as the platynecine ester sarracine and the orchid alkaloid phalaenopsine, that do not possess the unique necic acid moiety of the lycopsamine type, are sequestered by larvae but they need to be converted into the respective creatonotines and callimorphines by trans-esterification in order to be transferred to the adult stage. In the case of the orchid alkaloids, evidence is presented that during this processing the necine base (trachelanthamidine) is converted into its 7-(R)-hydroxy derivative (turneforcidine), indicating the ability of G. geneura to introduce a hydroxyl group at C-7 of a necine base. The creatonotines and callimorphines display a striking similarity to plant necine monoesters of the lycopsamine type to which G. geneura is well adapted. The possible function of insect-specific trans-esterification in the acquisition of necine bases derived from plant acquired alkaloids, especially from those that cannot be maintained through all life-stages, is discussed.     

New quinoline alkaloids from the leaves and stems of Orixa japonica, orijanone, isopteleflorine and 3'-O-methylorixine

Orixajaponica (Rutaceae) is a shrub widely distributed in Japan, and has been found to contain various quinoline alkaloids. We investigated the alkaloidal constituents of O. japonica, and four quinoline alkaloids were isolated and characterized. Three of these alkaloids are new natural products.     

Fungal grass endophytes and arthropod communities: lessons from plant defence theory and multitrophic interactions

Alkaloids produced by systemic fungal endophytes of grasses are thought to act as defensive agents against herbivores. Endophytic alkaloids may reduce arthropod herbivore abundances and diversity in agronomic grasses. Yet, accumulating evidence, particularly from native grasses, shows that herbivore preference, abundances and species richness are sometimes greater on endophyte-infected plants, even those with high alkaloids, contrary to the notion of defensive mutualism. We argue that these conflicting results are entirely consistent with well-developed concepts of plant defence theory and tri-trophic interactions. Plant secondary chemicals and endophytic alkaloids often fail to protect plants because: (1) specialist herbivores evolve to detoxify and use defensive chemicals for growth and survival; and (2) natural enemies of herbivores may be more negatively affected by alkaloids than are herbivores. Endophytes and their alkaloids may have profound, but often highly variable, effects on communities, which are also consistent with existing theories of plant defence and community genetics.     

Comparative study of the alkaloids in tribe Datureae and their chemosystematic significance

Sixty-six tropane alkaloids from crude leaf and root alkaloid mixtures of 12 different species and their varieties and subspecies from tribe Datureae were determined by GC–MS. The alkaloids 3β-hydroxy-6β-acetoxytropane, 3-propionyloxy-6-hyroxytropane, 3β-hydroxy-6β-tigloyloxytropane, 3β-tigloyloxy-6β-acetoxytropane and 3-tigloyloxy-7-isobutyryloxytropane are new reported tropane alkaloids.     

Alkaloid catabolism and mobilization in catharanthus roseus

The catabolic turnover of vindoline and catharanthine, indole-dihydroindole alkaloids produced by Catharanthus roseus, occurs much more rapidly in apical cuttings than in intact plants. The implication of the results is that such alkaloids may participate actively in the plant's biochemical processes under certain conditions, in contradistinction to the general belief that plant alkaloids are metabolically insignificant.     

The biosynthesis and genetic engineering of bioactive indole alkaloids in plants

Indole alkaloids are widely distributed secondary metabolites that exhibit a broad range of pharmacological activities. They are synthesized through plant biosynthetic pathways involving complex enzyme activities and regulatory strategies. Since many compounds of indole alkaloids are structurally too complex to be manufactured economically by chemical synthesis, they have to be isolated from naturally grown or cultivated plants. Therefore, the biotechnological production of high-value plant secondary metabolites in cultivated cells or transgenic plants is potentially an attractive alternative. The present review describes the regulation of indole alkaloids biosynthesis, as well as their pharmacological functions in plants such as anti-microbes, anti-inflammatory and anti-tumor. Furthermore, it discusses different strategies by which the genetic engineering of indole alkaloids biosynthesis through the reconstruction of the pathway achieves high production of specific compounds.     

Comparison of tropane alkaloid spectra between Datura innoxia grown in Egypt and Bulgaria

The alkaloid spectra of Datura innoxia plants grown in Egypt and Bulgaria were investigated by GC-MS. Thirty-eight alkaloids were detected in the roots, leaves and fruits of the plants. Five new alkaloids for D. innoxia are reported. Alkaloid spectra of Egyptian and Bulgarian plants differ significantly in respect to their alkaloid composition and main alkaloids accumulated in the plant organs.     

Biosynthesis and accumulation of ergoline alkaloids in a mutualistic association between Ipomoea asarifolia (Convolvulaceae) and a clavicipitalean fungus

Ergoline alkaloids occur in taxonomically unrelated taxa, such as fungi, belonging to the phylum Ascomycetes and higher plants of the family Convolvulaceae. The disjointed occurrence can be explained by the observation that plant-associated epibiotic clavicipitalean fungi capable of synthesizing ergoline alkaloids colonize the adaxial leaf surface of certain Convolvulaceae plant species. The fungi are seed transmitted. Their capacity to synthesize ergoline alkaloids depends on the presence of an intact differentiated host plant (e.g. Ipomoea asarifolia or Turbina corymbosa [Convolvulaceae]). Here, we present independent proof that these fungi are equipped with genetic material responsible for ergoline alkaloid biosynthesis. The gene (dmaW) for the determinant step in ergoline alkaloid biosynthesis was shown to be part of a cluster involved in ergoline alkaloid formation. The dmaW gene was overexpressed in Saccharomyces cerevisiae, the encoded DmaW protein purified to homogeneity, and characterized. Neither the gene nor the biosynthetic capacity, however, was detectable in the intact I. asarifolia or the taxonomically related T. corymbosa host plants. Both plants, however, contained the ergoline alkaloids almost exclusively, whereas alkaloids are not detectable in the associated epibiotic fungi. This indicates that a transport system may exist translocating the alkaloids from the epibiotic fungus into the plant. The association between the fungus and the plant very likely is a symbiotum in which ergoline alkaloids play an essential role.     

Cell types, microsymbionts, and pyridoacridine distribution in the tunic of three color morphs of the genus Cystodytes (Ascidiacea, Polycitoridae)

Abstract. The tunic of colonial ascidians of the genus Cystodytes is a dynamic and complex system where a variety of cell types and microsymbionts are found. The tunic is also the site where pyridoacridine alkaloids involved in chemical defense are found. We wanted to explore the composition of symbionts and tunic cell types and their relationship with localization of alkaloids in three color morphs (usually attributed to the species Cystodytes dellechiajei ). Tunic morphology was studied by means of transmission electron microscopy, and energy-dispersive X-ray microanalysis was performed for indirect localization of the bioactive alkaloids produced by these morphotypes. The main cell types identified are bladder cells, pigment cells, amebocytes, phagocytes, and morula cells. Amebocytes include several subtypes that may correspond to a sequence of ontogenetic stages; these cells also seem to give rise to other cell types. In the three morphotypes, the morphology of the tunic and tunic cells is basically the same. The alkaloids are localized in the pigment cells. At least three types of bacteria are present in the tunic, but they are scarce and do not store the targeted bioactive alkaloids. Our results indicate that, although pyridoacridine alkaloids are present in these ascidians, as in a variety of animal phyla, their wide taxonomic range is not necessarily the result of production by common microsymbionts, but rather of the convergent evolution of a successful biosynthetic pathway.     

Leaf herbivory and nutrients increase nectar alkaloids

Correlations between traits may constrain ecological and evolutionary responses to multispecies interactions. Many plants produce defensive compounds in nectar and leaves that could influence interactions with pollinators and herbivores, but the relationship between nectar and leaf defences is entirely unexplored. Correlations between leaf and nectar traits may be mediated by resources and prior damage. We determined the effect of nutrients and leaf herbivory by Manduca sexta on Nicotiana tabacum nectar and leaf alkaloids, floral traits and moth oviposition. We found a positive phenotypic correlation between nectar and leaf alkaloids. Herbivory induced alkaloids in nectar but not in leaves, while nutrients increased alkaloids in both tissues. Moths laid the most eggs on damaged, fertilized plants, suggesting a preference for high alkaloids. Induced nectar alkaloids via leaf herbivory indicate that species interactions involving leaf and floral tissues are linked and should not be treated as independent phenomena in plant ecology or evolution.     

Distribution of Benzylisoquinolines in Magnoliidae and Other Taxa

Based on the analysis of benzylisoquinoline alkaloids of 323 samples in 11 families, 50 genera and 181 species of the Chinese flora discussed in this paper are the biogenesis, evolution, distribution pattern and botanical sources as well as the pharmacological action of this specific category of alkaloids. Benzylisoquinoline alkaloids are found mainly in Magnoliidae, in which aporphines, bisbenzylisoquinolines and protoberberines are the three major types of the alkaloids. More specifically, aporphines appeare more concentrated in primitive woody plants such as the Annonaceae, while bisbenzylisoquinolines are especially common in the Menispermaceae, Thalictrum (the Ranunculaceae) and Berberis (the Berberidaceae). As to protoberberines, the quaternary ones occur mainly in the families Ranunculaceae and Berberidaceae, whereas the tertiary ones mainly in the relatively advanced families Menispermaceae and Papaveraceae within Magnoliidae. As a whole, a general rule can be drawn that the simpler the chemical structure of the benzylisoquinolines is, the more widely they are distributed in primitive groups; more specific ones only have a limited distribution in more advanced groups or even within one family or one to several genera. This general pattern of distribution of benzylisoquinoline alkaloids in plants may be of value as a taxonomic criterion for plant systematics. Furthermore, this group of alkaloids covers the gamut of pharmacologic responses, such as the antibacterial effect and the effect to cardiovascular and nervous systems, and consequently the correlation between benzylisoquinoline alkaloids and their pharmacologicactivities within Magnoliidae may worthily be applied for the finding of new drugs.