Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ALKALOIDS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1992

Chemistry of sulphur-bound pyrrolic metabolites in the blood of rats given different types of pyrrolizidine alkaloid.

Rats were injected with the pyrrolizidine alkaloids heliotrine, indicine, or anacrotine, and killed after 20 hr. Alkaloid metabolites conjugated to haemoglobin thiol groups were recovered in the form of pyrrolic monoethyl ethers, by treating blood samples with ethanolic silver nitrate under "buffered" conditions. Chemically prepared putative toxic metabolites of the alkaloids--dehydroheliotrine, dehydroindicine, and dehydroanacrotine--were also allowed to react in vitro with blood and with an immobilized thiol, thiol-Sepharose, and subsequently the S-conjugated pyrroles were again recovered as ethyl ethers. The recovered pyrrolic ethers were identified by comparing them with reference compounds prepared from ethanol and the dehydro-alkaloids, and the structures of the S-bound pyrroles were deduced. Blood from rats given the 9-monoester alkaloids heliotrine or indicine contained pyrrolic residues, S-bound at their 9-position. Anacrotine-treated rats yielded two diastereomeric 7-ethers, showing that dehydrocrotanecine 7-conjugates had been present in the blood. The products from alkaloid-treated rats were identical with those from blood or thiol-Sepharose treated with the corresponding dehydro-alkaloids in vitro. This supported the view that proximal metabolites leading to S-binding in vivo were the dehydro-derivatives of the alkaloids. In each case the thiols were attacked by the most reactive centre of the dehydro-alkaloid: the 9-ester in dehydroheliotrine and dehydroindicine, and the 7-ester in dehydroanacrotine. Accordingly, simple chemical reactions could account for the products formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Feeding responses to selected alkaloids by gypsy moth larvae, Lymantria dispar (L.).

Deterrent compounds are important in influencing the food selection of many phytophagous insects. Plants containing deterrents, such as alkaloids, are generally unfavored and typically avoided by many polyphagous lepidopteran species, including the gypsy moth Lymantria dispar (L.) (Lepidoptera: Lymantriidae). We tested the deterrent effects of eight alkaloids using two-choice feeding bioassays. Each alkaloid was applied at biologically relevant concentrations to glass fiber disks and leaf disks from red oak trees (Quercus rubra) (L.), a plant species highly favored by these larvae. All eight alkaloids tested on glass fiber disks were deterrent to varying degrees. When these alkaloids were applied to leaf disks, only seven were still deterrent. Of these seven, five were less deterrent on leaf disks compared with glass fiber disks, indicating that their potency was dramatically reduced when they were applied to leaf disks. The reduction in deterrency may be attributed to the phagostimulatory effect of red oak leaves in suppressing the negative deterrent effect of these alkaloids, suggesting that individual alkaloids may confer context-dependent deterrent effects in plants in which they occur. This study provides novel insights into the feeding behavioral responses of insect larvae, such as L. dispar, to selected deterrent alkaloids when applied to natural vs artificial substrates and has the potential to suggest deterrent alkaloids as possible candidates for agricultural use.

Alkaloids↗
PubMed1994

Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self-administration in rats. The present study sought to determine if other iboga alkaloids, as well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self-administration of morphine and cocaine in rats. Because both ibogaine and harmaline induce tremors, an effect that may be causally related to neurotoxicity in the cerebellar vermis, the temorigenic activities of the other iboga alkaloids were assessed. Lastly, in view of the involvement of the dopaminergic mesolimbic system in the actions of drugs of abuse, the effects of some of the iboga alkaloids on extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum were determined. All of the tested alkaloids (i.e., ibogaine, tabernanthine, R- and S-coronaridine, R- and S-ibogamine, desethylcoronaridine, and harmaline) dose-dependently (2.5-80 mg/kg) decreased morphine and cocaine intake in the hour after treatment; decreases in morphine and cocaine intake intake were also apparent the day after administration of some but not all of these alkaloids (i.e., ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine). In some rats, there were persistent decreases in morphine or cocaine intake for several days after a single injection or after two or three weekly injections of one or another of these alkaloids; R-ibogamine produced such effects more consistently than any of the other alkaloids.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1992

Variability in alkaloid profiles in neotropical poison frogs (Dendrobatidae): genetic versus environmental determinants.

Dendrobatid frogs produce a diverse set of alkaloids, whose profiles appear characteristic of frogs of each species or, in the case of variable species, of each population. In the case of one widespread species, Dendrobates auratus, alkaloid profiles in extracts of skin are markedly different in three populations, one from a Pacific island, Isla Taboga, Panama, one from central mountains in Panama, and the third from the Caribbean coast in Costa Rica. The first contains three major classes of dendrobatid alkaloids, the histrionicotoxins, the pumiliotoxin-A class and the decahydroquinolines. The second contains mainly histrionicotoxins, pumiliotoxin-A class alkaloids and one indolizidine. The third contains histrionicotoxins, a homopumiliotoxin, one decahydroquinoline, and a variety of indolizidines, quinolizidines and pyrrolizidines. Frogs from Isla Taboga or a nearby island were introduced into the Manoa Valley, Oahu, Hawaii, in 1932. Remarkably, although alkaloids of the pumiliotoxin-A class and one decahydroquinoline are still major constituents in skin extracts of Hawaiian frogs descended from the 1932 founding population, histrionicotoxins are absent and a novel tricyclic alkaloid is present. Offspring of wild-caught parents from Hawaii, Panama or Costa Rica raised in indoor terrariums on a diet of crickets and fruit flies do not contain detectable amounts of skin alkaloids. Offspring raised in large outside terrariums in Hawaii and fed mainly wild-caught termites and fruit flies do contain the same profile of alkaloids as their wild-caught parents in Hawaii, but at reduced levels. The genetic, environmental and dietary determinants of alkaloid profiles in dendrobatid frogs remain obscure, in particular the underlying cause for total absence in terrarium-reared frogs.

Alkaloids↗
PubMed1996

Metabolic activation of pyrrolizidine alkaloids by human, rat and avocado microsomes.

Two pyrrolizidine alkaloids and one pyrrolizidine alkaloid-N-oxide were incubated with microsomal preparations from humans, rat and avocado and the product profiles examined. The alkaloids were converted to dehydroretronecine, the putative toxic metabolite, by both rat and human microsomal preparations. In addition, alkaloid-N-oxides, the major detoxication products from pyrrolizidine alkaloids, were also formed. The pyrrolizidine alkaloid-N-oxide was converted to both dehydroretronecine and the parent alkaloid. This suggests that the toxicity of pyrrolizidine alkaloid-N-oxides could be greater than suggested hitherto as a result of conversion to the toxic metabolite via the parent alkaloid. Quantitative differences in the proportions of products formed by the different microsomal preparations may be of significance in the extrapolation of toxicological data from animal models such as the rat to humans.

Animals↗
PubMed1995

Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism.

The effect of total alkaloid extracted from Peganum harmala seeds collected in Egypt on body temperature was studied in rats. Intraperitoneal administration of the Peganum harmala extract produced significant and dose-dependent hypothermia. Similarly, harmine and harmaline, major constituents of the harmala alkaloid, lowered the body temperature. Pretreatment with p-chlorophenylalanine (100 mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the hypothermic effect of the total alkaloid and harmine, while it tended to block the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist, significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol (0.05-2 mg/kg), a 5-HT1A receptor and beta-adrenoceptor antagonist, partly blocked the hypothermic effect of the harmala alkaloids in a dose-dependent manner, whereas propranolol (10 mg/kg), a beta-adrenoceptor antagonist, failed to alter it, suggesting that beta-adrenoceptor is not involved in the hypothermia caused by the alkaloids. Pretreatment with a dopamine receptor antagonist haloperidol (5 mg/kg, s.c. and 2 mg/kg, i.p. 24 and 2 h before the experiment, respectively) significantly attenuated the hypothermic effect of harmala alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, i.p.) and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of the alkaloids. These data suggest that harmala alkaloids produce hypothermic effect mainly through endogenous 5-HT stimulation of 5-HT1A receptor.

Adrenergic beta-Antagonists↗
PubMed1991

Effect of culture process on alkaloid production by Catharanthus roseus cells. II. Immobilized cultures.

Two processes for the production of indole alkaloids 2 l surface-immobilized bioreactor cultures of Catharanthus roseus cells using Zenk's Alkaloid Production Medium (APM) were evaluated. The 1-stage process consisted of inoculating APM containing bioreactors and incubating for 15 d. The 2-stage process involved inoculating growth medium-containing bioreactors, growing the immobilized cultures for a certain period of time and subsequently replacing this medium with APM. The production stage which lasted for 15 d. High production in 2-stage cultures required the replacement of the growth regulator 2,4-dichlorophenoxyacetic acid by indole-3-acetic acid in the growth medium and a growth stage of 6 d (late exponential phase) before production initiation. Growth, main nutrient consumption and alkaloid production were monitored. Both culture regimes resulted in similar biomass production, dw (10-13 g l-1). The 2-stage cultures yielded biomass richer in organic nutrients (200-300%) and with higher respiratory activity (approximately 250%), indicated by their lower biomass-to-carbohydrate yields (31% and 26%), as compared to 1-stage cultures (41%). Two-stage cultures produced more known products (10 as compared to 6) at yields (5 to 4800 micrograms g-1) 3 to 5 times higher than 1-stage cultures. More alkaloids were alkaloids released in the medium of 2-stage cultures, under non-lysing conditions, (20 to 4700 micrograms l-1) than in 1-stage cultures (20 to 460 micrograms l-1). These results were compared to those obtained from shake flask cultures performed at the same time, with the same C. roseus cell line and under similar regimes and reported previously. Suspension and immobilized cultures performed according to the 1-stage regime showed similar total production. However, release of known alkaloids was 2 to 3 times higher in immobilized than in suspension cultures. Total alkaloid production of 2-stage suspension cultures was 3.8-fold higher than 2-stage immobilized cultures. Two stage immobilized cultures released 4 more known alkaloids than the 2-stage suspensions. Lower oxygen availability in the 2 l immobilized cultures may explain lower specific growth rates (0.15-0.22 d-1) and total alkaloid production levels, compared to 200 ml suspension cultures (0.2-0.4 d-1) reported in our previous paper.

Alkaloids↗
PubMed1992

Detection of sulphur-conjugated pyrrolic metabolites in blood and fresh or fixed liver tissue from rats given a variety of toxic pyrrolizidine alkaloids.

Rats were given single injections of hepatotoxic pyrrolizidine alkaloids and killed after 30 h. Sulphur-bound pyrrolic metabolites from the alkaloids in samples of their blood or liver tissue were converted to extractable ethyl ethers of low molecular weight for detection and identification using TLC, HPLC or GC-MS. Liver samples were also preserved as an acetone-washed powder or in formalin-based fixative before being later subjected to similar analyses. S-Bound pyrrolic metabolites were identified in samples from rats given all the types of alkaloid tested, which included mono-esters (heliotrine, indicine), a diester (lasiocarpine), and macrocyclic diesters (retrorsine, senecionine). The pattern of pyrrolic metabolites from the crotanecine-based alkaloid anacrotine differed and could be distinguished from retronecine- or heliotridine-based alkaloids. Whereas the alkaloids tested ranged widely in toxicity, single doses of 0.25 x acute LD50 or more led to detectable metabolites. Liver pyrroles remained detectable in fixed or powdered samples preserved for long periods. Similar tests on rats given monocrotaline continuously in their drinking water (20 mg/l) led to detectable pyrroles in blood after 12 days (total intake approx. 27 mg/kg) and in liver after 25 days. The metabolites remained detectable in rats killed 17 days after the alkaloid exposure was discontinued. The simple procedures described are applicable to the diagnosis of pyrrolizidine alkaloid exposure in livestock, using fresh or dried blood or fresh or preserved liver samples. They bring to pyrrolizidine toxicology for the first time the capability to demonstrate chemically that livestock (or people) have been exposed to these alkaloids many days or weeks previously.

Animals↗
PubMed1986

Preliminary phytochemical, pharmacological and antibacterial studies of the alkaloidal extracts of the leaves of Synclisia scabrida Miers.

Preliminary phytochemical investigation of the leaves of Synclisia scabrida indicated the presence of two alkaloids in the water extracts and five alkaloids in the ethanol extracts. The alkaloidal fraction obtained from the cold ethanol extract furnished on column-chromatography, a homogeneous amorphous solid which has been designated as alkaloid C. Alkaloid C showed positive test for alkaloids. The UV and IR spectra and colour reactions of alkaloid C indicated that the compound may be a phenolic bisbenzylisoquinoline alkaloid. All the extracts delayed the onset and shortened the duration of apomorphine-induced stereotyped behaviour in chicks. In addition, 40 mg kg-1 i.p. of the ethanolic extract induced catalepsy in rats. The cold water extract (CWE) synchronized the EEG of the hyperstriatum, optic tectum and the reticular formation while the EMG activity was slightly enhanced. The hot ethanol alkaloidal extract (HEE) inhibited the growth of Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration of HEE on Pseudomonas aeruginosa strains I and II were 5 and 2.5 micrograms/ml while for Staphylococcus aureus strains I and II were 5 and 10 micrograms/ml, respectively. Up to 1 g kg-1 i.p. of the extract failed to induce any lethal effect in chicks and rats. These effects of the leaf extracts of Synclisia scabrida Miers support some of the local uses of the plant by traditional medical practitioners.

Alkaloids↗
PubMed1991

Studies on the constituents of Aconitum species. IX. The pharmacological properties of pyro-type aconitine alkaloids, components of processed aconite powder 'kako-bushi-matsu': analgesic, antiinflammatory and acute toxic activities.

Eight pyro-type aconitine alkaloids contained in the processed aconite powder 'Kako-bushi-matsu' were studied for their analgesic, antiinflammatory and acute toxic actions. All these compounds showed significant analgesic and antiinflammatory actions. Among the pyro-type alkaloids, 16-epi-pyrojesaconitine and pyrojesaconitine were the most potent analgesics. The analgesic activity of pyro-type aconitine alkaloids was lower than that of each of the parent alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine. However, pyro-type aconitine alkaloids had very low toxicity, and the decreasing rates of the toxicity in changing from the parent alkaloids to the pyro-type aconitine alkaloids were much larger than those relating to the analgesic activity. Eight pyro-type aconitine alkaloids were found to inhibit the carrageenin-induced hind paw edema at 2 to 6 h after the carrageenin subplantar injection. Consequently, it was demonstrated that the pyro-type aconitine alkaloids produced through the processing of raw aconite roots, 'Bushi', have a role in the medicinal effects of the processed aconite powder 'Kako-bushi-matsu'.

Aconitine↗
PubMed2005

Specific recognition, detoxification and metabolism of pyrrolizidine alkaloids by the polyphagous arctiid Estigmene acrea.

Evidence is presented that the polyphagous arctiid Estigmene acrea is well adapted to sequester and specifically handle pyrrolizidine alkaloids of almost all known structural types representative of the major plant families with pyrrolizidine alkaloid-containing species, i.e. Asteraceae with the tribes Senecioneae and Eupatorieae, Boraginaceae, Fabaceae, Apocynaceae and Orchidaceae. The adaptation of E. acrea to pyrrolizidine alkaloids includes a number of specialized characters: (i) highly sensitive recognition of alkaloid sources by pyrrolizidine alkaloid-specific taste receptors; (ii) detoxification of pyrrolizidine alkaloids by N-oxidation catalyzed by a specific flavin-dependent monooxygenase; (iii) transfer and maintenance of all types of pyrrolizidine N-oxides through all developmental stages; (iv) conversion of the various structures into the male courtship pheromone hydroxydanaidal most probably through retronecine and insect specific retronecine esters (creatonotines) as common intermediates; (v) specific integration into mating behavior and defense strategies. Toxic otonecine derivatives, e.g. the senecionine analogue senkirkine, which often accompany the common retronecine derivatives and which cannot be detoxified by N-oxidation do not affect the development of E. acrea larvae. Senkirkine is not sequestered at all. Non-toxic 1,2-saturated platynecine derivatives that frequently occur together with toxic retronecine esters are sequestered and metabolized to hydroxydanaidal, indicating the ability of E. acrea to aromatize saturated pyrrolizidines. Although pyrrolizidine alkaloids, even if they are offered continuously at a high level (2%) in the larval diet, are non-toxic, E. acrea larvae are not able to develop exclusively on a pyrrolizidine alkaloid-containing plant like Crotalaria. Therefore, E. acrea appears to be specifically adapted to exploit pyrrolizidine alkaloid-containing plants as "drug source" but not as a food source.

Animals↗
PubMed1998

Involvement of protein kinase and G proteins in the signal transduction of benzophenanthridine alkaloid biosynthesis.

We have previously reported that elicitor-induced benzophenanthridine alkaloid biosynthesis in suspension-cell cultures of Sanguinaria canadensis L. (SCP-GM) is mediated by a signal transduction system that involves calcium and possibly protein kinase(s). In this work, a number of exogenous agents were employed to further investigate the components of the signal transduction pathway involved in the induction of alkaloid biosynthesis by a fungal elicitor and abscisic acid (ABA). SCP-GM suspension-cells were treated with compounds that modify protein kinase activity, including phorbol esters, and 1-oleoyl-2-acetyl-rac-glycerol (OAG), a synthetic diacylglycerol analogue. Phorbol-12-myristate-13-acetate induced alkaloid accumulation by as much as 65-fold over control values, while the negative control, phorbol-13-monoacetate, had no effect. OAG also increased alkaloid production by approximately 25-fold as compared to controls. Likewise, pretreatment of the suspension-cell cultures with H-7 or staurosporine, significantly suppressed ABA- or fungal-induction of benzophenanthridine alkaloid biosynthesis. Modulators of GTP-binding protein activity were also active in this system. Treatment of the suspension-cells with cholera toxin (CHX) induced alkaloid accumulation by 25-fold, which increased to 34-fold when CHX was combined with a fungal elicitor derived from Penicillium expansum (PE), and 32-fold when CHX was combined with ABA. Treatment of SCP-GM cells with CHX also enhanced the activities of two N-methyltransferases in the benzophenanthridine biosynthetic pathway namely, tetrahydroberberine-N-methyltransferase and tetrahydrocoptisine-N-methyltransferase, by six and seven fold, respectively. Furthermore, benzophenanthridine alkaloid biosynthesis was induced by treating the suspension-cells with the G-protein activators, mastoparan, mas-7 or melittin, while the inactive homologue, mas-17, did not. Suppression of alkaloid accumulation occurred when the suspension-cells were treated with GDP beta S or pertussis toxin prior to treatment of the SCP-GM cells with either PE or ABA. The results support the hypothesis that one or more protein kinases, and putative G proteins are involved in the signal transduction pathway that mediates ABA and fungal-induced benzophenanthridine alkaloid biosynthesis.

Abscisic Acid↗
PubMed2001

Sequestration, metabolism and partial synthesis of tertiary pyrrolizidine alkaloids by the neotropical leaf-beetle Platyphora boucardi.

Platyphora boucardi leaf-beetles sequester tertiary pyrrolizidine alkaloids of the lycopsamine type acquired from their host-plant Prestonia portobellensis (Apocynaceae) and synthesize their own alkaloids from exogenous retronecine and aliphatic 2-hydroxy acids. Tracer studies with [14C]rinderine and its N-oxide revealed that P. boucardi sequesters both alkaloidal forms with the same efficiency, but accumulates exclusively tertiary alkaloids. There is no substantial alkaloid accumulation in the body outside the defensive glands. Feeding studies with [2H][14C]rinderine confirmed that P. boucardi specifically epimerizes rinderine to its stereoisomers intermedine and lycopsamine. Feeding studies with [2H][14C]retronecine proved the ability of P. boucardi to synthesize O7- and O9-(2-hydroxyisovaleryl)-retronecine and O7-lactyl-O9-(2-hydroxyisovaleryl)-retronecine. Both, alkaloids of the lycopsamine type and self-synthesized retronecine esters accumulate in the defensive secretions at concentrations up to 38 mM and 33 mM, respectively. The different biochemical strategies to maintain pro-toxic pyrrolizidine alkaloids and to prevent self-poisoning, developed by specialized insects, are compared. There are two major findings: (1) the chemical defense mediated by plant acquired pyrrolizidine alkaloids in the taxonomically related palaearctic Oreina and neotropical Platyphora leaf beetles have been evolved independently, since the biochemical mechanisms of storing and maintaining the alkaloids is completely different in the two genera; (2) unexpected parallels exist between taxonomically unrelated Coleoptera and Lepidoptera in their ability to synthesize the same retronecine esters and to catalyze the same site-specific epimerizations of the lycopsamine stereoisomers.

Animals↗
PubMed2003

Biochemical processing of plant acquired pyrrolizidine alkaloids by the neotropical leaf-beetle Platyphora boucardi.

Leaf beetles of the genus Platyphora, feeding on plant species containing pyrrolizidine alkaloids of the lycopsamine type, not only sequester these alkaloids and concentrate them in their exocrine defensive secretions, but also specifically process the plant acquired alkaloids. Using P. boucardi as subject, three mechanisms were studied: (i). utilization of host plant alkaloids that are not sequestered per se; (ii). elucidation of the mechanism of the already documented C-7 epimerization of heliotridine O(9)-monoesters; (iii). the specificity of insect catalyzed necine base esterification. P. boucardi does not sequester the triester parsonsine, the principal alkaloid of its host plant Prestonia portobellensis (Apocynaceae). Beetles fed with a purified mixture of nor-derivatives of parsonsine, obtained from Parsonsia laevigata, did not sequester the triesters but transformed them by partial degradation into monoesters that are accumulated in the defensive secretions. The mechanism of the previously described transformation of rinderine into intermedine by C-7 epimerization was elucidated by feeding C-7 deuterated heliotrine (3'-methylrinderine). The transformation of heliotrine into epiheliotrine (3'-methylintermedine) catalyzed by P. boucardi is accompanied by complete loss of deuterium, indicating the same mechanism of an oxidation-reduction process via a ketone intermediate as recently demonstrated in a pyrrolizidine alkaloid sequestering lepidopteran. P. boucardi is able to form ester alkaloids from five different necine bases fed as radioactively labeled substrates. However, besides C-7 epimerization the beetles are not able to convert simple necine bases into retronecine. The functional importance of the various alkaloid transformations is discussed in comparison to striking parallels of analogous reactions known from pyrrolizidine alkaloid sequestering Lepidoptera.

Animals↗
PubMed2003

Modulation of berberine bridge enzyme levels in transgenic root cultures of California poppy alters the accumulation of benzophenanthridine alkaloids.

California poppy (Eschscholzia californica Cham.) root cultures produce a variety of benzophenanthridine alkaloids, such as sanguinarine, chelirubine and macarpine, with potent biological activity. Sense and antisense constructs of genes encoding the berberine bridge enzyme (BBE) were introduced into California poppy root cultures. Transgenic roots expressing BBE from opium poppy (Papaver somniferum L.) displayed higher levels of BBE mRNA, protein and enzyme activity, and increased accumulation of benzophenanthridine alkaloids compared to control roots transformed with a beta-glucuronidase gene. In contrast, roots transformed with an antisense-BBE construct from California poppy had lower levels of BBE mRNA and enzyme activity, and reduced benzophenanthridine alkaloid accumulation, relative to controls. Pathway intermediates were not detected in any transgenic root lines. Suppression of benzophenanthridine alkaloid biosynthesis using antisense-BBE also reduced the growth rate of the root cultures. Two-dimensional 1H-NMR spectroscopy showed no difference in the abundance of carbohydrate metabolites in the various transgenic roots lines. However, transformed roots with low levels of benzophenanthridine alkaloids contained larger cellular pools of certain amino acids compared to controls. In contrast, cellular pools of several amino acids were reduced in transgenic roots with elevated benzophenanthridine alkaloid levels relative to controls. The relative abundance of tyrosine, from which benzophenanthridine alkaloids are derived, was only marginally altered in all transgenic root lines; thus, altering metabolic flux through benzophenanthridine alkaloid pathways can affect cellular pools of specific amino acids. Consideration of such interactions is important for the design of metabolic engineering strategies that target benzophenanthridine alkaloid biosynthesis.

Alkaloids↗
PubMed2004

The Lycopodium alkaloids.

Lycopodium alkaloids are quinolizine, or pyridine and alpha-pyridone type alkaloids. Some Lycopodium alkaloids are potent inhibitors of acetylcholinesterase (AChE). Huperzine A (HupA) is reported to increase efficiency for learning and memory in animals, and it shows promise in the treatment of Alzheimer's disease (AD). 201 Lycopodium alkaloids from 54 species of Lycopodium (sensu lato) have been reported so far. This review is intended to to cover the chemical, pharmacological and clinical research on Lycopodium alkaloids reported in the literature from the spring of 1993 to August 2004. Structures of 81 new Lycopodium alkaloids are presented, classified and analyzed. The structural characters and biogenetic relationships of the four major Lycopodium alkaloid groups (lycopodine, lycodine, fawcettimine and miscellaneous) are discussed. Bioactivities of Lycopodium alkaloids, especially HupA, are summarized. In particular, the effect of HupA and other cholinesterase inhibitors (anti-AD drugs) on acetylcholine esterase (AChE) activity in the rat cortex and butylcholine esterase activity are compared. Structure-activity relationships and structure modifications of HupA and its analogs are described. Information on clinical trials with HupA and its derivative ZT-1 is presented. The state of HupA availability and recent advances in in vitro propagation of HupA producing plants are outlined. Finally, hypotheses about Lycopodium alkaloid biosynthetic pathways are discussed.

Alkaloids↗
PubMed2000

Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots.

The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines.

Alkaloids↗
PubMed2000

Chemical defense: bestowal of a nuptial alkaloidal garment by a male moth on its mate.

Males of the moth Cosmosoma myrodora (Arctiidae) acquire pyrrolizidine alkaloid by feeding on the excrescent fluids of certain plants (for instance, Eupatorium capillifolium). They incorporate the alkaloid systemically and as a result are protected against spiders. The males have a pair of abdominal pouches, densely packed with fine cuticular filaments, which in alkaloid-fed males are alkaloid laden. The males discharge the filaments on the female in bursts during courtship, embellishing her with alkaloid as a result. The topical investiture protects the female against spiders. Alkaloid-free filaments, from alkaloid-deprived males, convey no such protection. The males also transmit alkaloid to the female by seminal infusion. The systemic alkaloid thus received, which itself may contribute to the female's defense against spiders, is bestowed in part by the female on the eggs. Although paternal contribution to egg defense had previously been demonstrated for several arctiid moths, protective nuptial festooning of a female by its mate, such as is practiced by C. myrodora, appears to be without parallel among insects.

Animals↗