Special Issue "Ergot Alkaloids: Chemistry, Biology and Toxicology"
A special issue of Toxins (ISSN 2072-6651).
Deadline for manuscript submissions: 31 October 2014
Prof. Dr. Christopher L. Schardl
Department of Plant Pathology, University of Kentucky 201C Plant Science Building, Lexington, KY 40546-0312, USA
Website: http:// http://www2.ca.uky.edu/agcollege/plantpathology/people/schardl.htm
Phone: (859) 218-0730
Fax: (859) 323-1961
Interests: natural products biochemistry, genomics, mycology, plant-fungus symbiosis
Alkaloids encompass a wide diversity of nitrogen-containing specialized (secondary) metabolites, which are often associated with plants and provide defense against herbivores, pathogens and parasites. A class of alkaloids of particular relevance to human society, medicine and agriculture is the ergot alkaloids, so named because many ergot fungi (Claviceps species) produce these metabolites in abundance. Ergot alkaloids are known from plant-symbiotic and plant-pathogenic fungi in family Clavicipitaceae (phylum Ascomycota), from other orders of fungi, and from other biological sources. They range in size and complexity from the tricyclic and tetracyclic clavines to the hexacyclic and heptacyclic ergopeptines. Though some are cytotoxic and antimicrobial, most are primarily neurotropic. Ergot alkaloids can occur in grains contaminated by sclerotia (ergots) of Claviceps species, or in forage grasses, and morning glory plants where they are produced by endophytic fungi. Ingestion of ergot alkaloids causes poisonings described as convulsive or gangrenous ergotism depending on the forms of the alkaloids. On the other hand, at appropriate doses, and sometimes in modified forms, ergot alkaloids are useful as pharmaceuticals, including ergonovine (= ergometrine) in childbirth, ergotamine for migraines, and bromocryptine for Parkinson’s disease. The serendipitous discovery of a particularly hallucinogenic derivative, lysergic acid diethylamide (LSD), played a major role in the Western counterculture of the 1960s and 1970s. The ergot alkaloid biosynthetic pathway, the enzymes involved, and the genes encoding those enzymes have largely been elucidated. Evolutionary diversification of ergot alkaloids stems from changes in substrate and product specificity of some key enzymes, as well as acquisition and losses of genes for biosynthesis and modification enzymes. Fungi with functional ergot alkaloid pathways can have as few as four genes for chanoclavine biosynthesis, or as many as 14 genes for production of an array of lysergic acid amides and ergopeptines. This special issue will address the following aspects of ergot alkaloids:
1. Biosynthetic pathways: Clavines
2: Biosynthetic pathways: Lysergic acid amides and ergopeptines
3. Chemical diversity: Enzyme specificities
4. Chemical diversity: Genetics, genomics and evolution
5. Activities and effects: Humans and small animals
6. Activities and effects: Livestock
Prof. Dr. Christopher L. Schardl
- ergot alkaloids
- natural products
- secondary metabolism
- biosynthetic pathways
- food safety
- livestock health
- pasture management
- forage plants
- poisonous plants
- therapeutic drugs
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Authors: Michel Andrjak, Service de Pharmacologie Clinique
Abstract: Fibrosis with different localisations have been reported after long term exposure to several ergot alkaloid derivatives such as methysergide, ergotamine, pergolide and cabergoline used in various medical diseases such as migraine Parkinson’s disease, hyperprolactinemia cognitive and sensorineural deficits in elderly patients. Fibrosis is involved in severe adverse effects such valvular heart disease pulmonary hypertension, pericardial, pleural, pulmonary as well as retroperitoneal fibrosis.
The relative similarity of ergot alkaloid derivatives linked valvular heart disease with carcinoid heart disease has been the first reason to suspect the role of serotoninergic mechanisms in the development of fibrotic complications linked to mitogenic effects on fibroblasts and smooth muscle cells. The role of the activation of some serotoninergic receptors identified as 5HT2B receptors has been evidenced, and also reported with other drug such fenfluramine, dexfenfluramine, benfluorex and ecstasy also caracterized as having marked 5HT2B agonist properties. Some ergot derivatives such as lisuride and tergitide having no agonist (but antagonist) properties on 5HT2B receptors are not associated with the development of fibrotic reactions.
Conclusions. Fibrotic reactions may appear during long-term exposure to some ergot alkaloid derivatives and may lead to severe complications. These reactions occur only in ergot derivatives having 5HT2B agonist properties.
Last update: 28 August 2014