The Alkaloids: Chemistry and Biology 

About: The Alkaloids: Chemistry and Biology is an academic journal published by Elsevier BV. The journal publishes majorly in the area(s): Ibogaine & Indole test. It has an ISSN identifier of 1099-4831. Over the lifetime, 148 publications have been published receiving 3716 citations. The journal is also known as: Alkaloids Chem Biol & Alkaloids, Chem. biol..

Ergot alkaloids--biology and molecular biology.

Abstract: EA have been a major benefit, and a major detriment, to humans since early in recorded history Their medicinal properties have been used, and continue to be used, to aid in childbirth, with new uses being found in the treatment of neurological and cardiovascular disorders The surprisingly broad range of pharmaceutical uses for EA stems from their affinities for multiple receptors for three distinct neurotransmitters (serotonin, dopamine, and adrenaline), from the great structural diversity of natural EA, and from the application of chemical techniques that further expand that structural diversity The dangers posed by EA to humans and their livestock stem from the ubiquity of ergot fungi (Claviceps species) as parasites of cereals, and of related grass endophytes (Epichloe, Neotyphodium, and Balansia species) that may inhabit pasture grasses and produce toxic levels of EA Further concerns stem from saprophytic EA producers in the genera Aspergillus and Penicillium, especially A fumigatus, an opportunistic pathogen of humans Numerous fungal species produce EA with a wide variety of structures and properties These alkaloids are associated with plants in the families Poaceae, Cyperaceae, and Convolvulaceae, apparently because these plants can have symbiotic fungi that produce EA Pharmacological activities of EA relate to their specific structures Known as potent vasoconstrictors, the ergopeptines include a lysergic acid substituent with an amide linkage to a complex cyclol-lactam ring structure generated from three amino acids Simpler lysergyl amides and clavines are more apt to have oxytonic or psychotropic activities One of the lysergyl amides is LSD (5), the most potent hallucinogen known The EA biosynthetic pathway in Claviceps species has been studied extensively for many decades, and recent studies have also employed epichloes and A fumigatus The early pathway, shared among these fungi, begins with the action of an aromatic prenyl transferase, DMATrp synthase, which links a dimethylallyl chain to L-tryptophan When the dmaW gene encoding DMATrp synthase was cloned and sequenced, the predicted product bore no identifiable resemblance to other known prenyl transferases The dma W genes of Claviceps species are present in clusters of genes, several of which also have demonstrated roles in EA biosynthesis In many other fungi, dma W homologues are identifiable in otherwise very different gene clusters The roles of DMA Trp synthase homologues in these other fungi are probably quite variable One of them is thought to prenylate the phenolic oxygen of L-tyrosine, and another catalyzes the unusual reverse prenylation reaction in the biosynthesis of fumigaclavine C(10), an EA characteristic of A fumigatus The second step of the EA pathway is N-methylation of DMATrp (12) to form 13, which is then subjected to a series of oxidation/oxygenation and reduction reactions to generate, in order, chanoclavine-I (16), agroclavine (19), and elymoclavine (6) Shunt reactions generate a wide variety of other clavines Two epimerizations occur in this pathway: one from 12 to 16, the other from 16 to 19 Further oxidation of 6, catalyzed by the cytochrome-P450 CloA, generates lysergic acid (1) An unusual NRPS complex, lysergyl peptide synthetase (LPS), is responsible for linking 1 to three hydrophobic L-amino acids to generate the ergopeptide lactams The LPS complex includes two polypeptides, one (LPS 2) possessing a single module for activation of 1, and the other (LPS 1) possessing three modules, each specifying one of the L-amino acids Variations in LPS 1 sequences are associated with variations in the incorporated amino acids, leading to differences between strain chemotypes, and even multiple ergopeptines within strains For example, C purpurea P1 produces two distinct ergopeptines (ergotamine (4) and ergocryptine (Table I)), each of which is believed to be generated by multiple LPS 1 subunits encoded by separate, but related, genes (lpsA1 and lpsA2) The main ecological roles of EA in nature are probably to protect the fungi from consumption by vertebrate and invertebrate animals The EA produced by plant-symbiotic fungi (such as epichloe endophytes) may protect the fungus by protecting the health and productivity of the host, which may otherwise suffer excessive grazing by animals The EA, at levels typical of plants bearing these symbionts, can negatively affect the health of large mammals as well herbivorous insects Some clavines have substantial anti-bacterial properties, which might protect the fungus and, in some cases, their host plants from infection However, the fact that a large number of epichloe, and even several Claviceps species, produce no detectable EA indicates that the selection for their production is not universal An unfortunate fact for many livestock producers is that some of the most popular forage grasses tend to possess EA-producing epichloe endophytes Such endophytes are easily eliminated, but confer such fitness enhancements to their hosts that their presence is often preferred, despite the toxic EA The future looks promising for continued interest in EA Research continues into their pharmacological properties, medicinal uses, and structure-function relationships New clavines and lysergic acid derivatives are identified regularly from new sources, such as marine animals Also, programs are well underway to modify or replace epichloe endophytes of forage grasses in order to produce new grass cultivars that lack these toxins

Nitrogen-containing metabolites from marine cyanobacteria.

Abstract: Publisher Summary Marine cyanobacteria are extraordinarily prolific in their elaboration of complex and bioactive secondary metabolites. The principle biogenetic theme in the natural products chemistry of marine cyanobacteria is the integration of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) pathways, in a variety of configurations, so as to produce this great structural diversity. An assortment of unusual “tailoring” enzymes is evident in cyanobacterial metabolites, as revealed by the variety of bromine and chlorine functional groups. Methylation is a prominent characteristic of most marine cyanobacterial metabolites. Cyanobacterial peptides possess an extremely high level of N -methylation, a characteristic that could possibly be advantageous in molecular genetic studies. In polyketide sections, a pronounced theme of pendant methyl groups is also evident. However, available experimental evidence suggests either a or C-2 of acetate origin for these methyl group additions. Many marine cyanobacterial metabolites possess potent biological properties.

C20-diterpenoid alkaloids

Abstract: Publisher Summary This chapter discusses the classification, distribution, and occurrence; biosynthesis and biogenesis; stereochemistry and reactions; and pharmacology of C 20 -diterpenoid alkaloids. With respect to the carbon skeleta, the C 20 -diterpenoid alkaloids may be divided into four classes: (1). Atisane-class: considered as the derivatives of aminated atisanes; (2) Kaurane-class: consided as the derivatives of aminated kauranes; (3) Rearranged-class: with a new heterocyclic skeleton formed by rearrangement of the hetisine- or denudatine-types; (4). Bisditerpcnoid-class: with the carbon skeleton of 40 or 39 carbon atoms—that is, by condensation of two Czo-diterpenoid alkaloids, or of one each of the C 20 - and C 19 -diterpenoid alkaloids. The richest sources of C 20 -diterpenoid aIkaloids are the plants of the two genera Aconitum and Delphinium in the Ranunculaceac and of the genus Spiraea in the Rosaceae. A sizable number of the C 20­ - diterpenoid alkaloids were isolated from the several Spiraea plants due to the Chinese scientists Liang and Hao. In addition, one interesting advance in the field is that three known C 20 -diterpenoid alkaloids acorientine, orientinine, and panicudine were identified from the epigeal parts of Rumex pictus by the Egyptian scientist Salama.

Ibogaine: a review.

Abstract: Publisher Summary The chapter discusses ibogaine, which is a naturally occurring plant alkaloid with a history of use as a medicinal and ceremonial agent in West Central Africa and has been alleged to be effective in the treatment of drug abuse. The National Institute on Drug Abuse (NIDA) has given significant support to animal research, and the U.S. Food and Drug Administration (FDA) has approved Phase I studies in humans. The chapter discusses the first International Conference on Ibogaine. A major focus of the Conference was the possible mechanism(s) of action of ibogaine. Another important focus of the Conference was to discuss human experience with ibogaine and preclinical and clinical evidence of efficacy and safety. The Conference also featured presentations related to the sociological and anthropological aspects of the sacramental context of the use of iboga in Africa and the distinctive ibogaine subculture of the U.S and Europe. Ibogaine is the most abundant alkaloid in the root bark of the Apocynaceous shrub Tabernanthe iboga , which grows in West Central Africa. The chapter presents a timeline that outlines the historical events relating to the development of ibogaine as a treatment for drug dependence. Ibogaine and serotonin both contain an indole ring in their structure, and ibogaine has been shown to bind to the serotonin transporter and to increase serotonin levels in the nucleus accumbens (NAc). Stereotypy is a methodologic issue that might explain some of the disparate results regarding ibogaine's interaction with the locomotor response to cocaine.

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

Abstract: Publisher Summary This chapter discusses the chemical and biological aspects of Narcissus alkaloids. Numerous alkaloids have been isolated from Narcissus speciesasaresult of the continuing search for novel alkaloids with pharmacological activity in the Amaryllidaceae family. The alkaloids isolated from this genus, classified in relation to the different skeleton types. The different Narcissus wild species and intersectional hybrids, grouped into subgenera and sections, with their corresponding alkaloids, arranged according to their ring system are listed. The biosynthetic pathways of Narcissus alkaloids includes: (1) enzymatic preparation of the precursors, (2) primary cyclization mechanisms, (3) enzymatic preparation of intermediates, (4) secondary cyclization, diversification, and restructuring. The chapter discusses proton nuclear magnetic resonance ( 1 H NMR), carbon nuclear magnetic resonance ( 13 C NMR), and mass spectrometry (MS) for Narcissus alkaloids. A list of the different Narcissus alkaloids, their spectroscopic properties, and literature with the most recent spectroscopic data is given. Several Narcissus extracts shows the following activities: antiviral, prophage induction, antibacterial, antifungal, antimalarial, insecticidal, cytotoxic, antitumor, antimitotic, antiplatelet, hypotensive, emetic, acetylcholine esterase inhibitory, antifertility, antinociceptive, chronotropic, pheromone, plant growth inhibitor, and allelopathic.