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      Reviewing Colchicaceae Alkaloids – Perspectives of Evolution on Medicinal Chemistry

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          Abstract

          The subject of chemosystematics has provided insight to both botanical classification and drug development. However, degrees of subjectivity in botanical classifications and limited understanding of the evolution of chemical characters and their biosynthetic pathways has often hampered such studies. In this review an approach of taking phylogenetic classification into account in evaluating colchicine and related phenethylisoquinoline alkaloids from the family Colchicaceae will be applied. Following on the trends of utilizing evolutionary reasoning in inferring mechanisms in eg. drug resistance in cancer and infections, this will exemplify how thinking about evolution can influence selection of plant material in drug lead discovery, and how knowledge about phylogenetic relationships may be used to evaluate predicted biosynthetic pathways.

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          Plant defense against herbivores: chemical aspects.

          Axel Mithöfer, Wilhelm Boland (2012)
          Plants have evolved a plethora of different chemical defenses covering nearly all classes of (secondary) metabolites that represent a major barrier to herbivory: Some are constitutive; others are induced after attack. Many compounds act directly on the herbivore, whereas others act indirectly via the attraction of organisms from other trophic levels that, in turn, protect the plant. An enormous diversity of plant (bio)chemicals are toxic, repellent, or antinutritive for herbivores of all types. Examples include cyanogenic glycosides, glucosinolates, alkaloids, and terpenoids; others are macromolecules and comprise latex or proteinase inhibitors. Their modes of action include membrane disruption, inhibition of nutrient and ion transport, inhibition of signal transduction processes, inhibition of metabolism, or disruption of the hormonal control of physiological processes. Recognizing the herbivore challenge and precise timing of plant activities as well as the adaptive modulation of the plants' metabolism is important so that metabolites and energy may be efficiently allocated to defensive activities.
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            A revised system of classification of the angiosperms

            R. DAHLGREN (1980)
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              Mining the biodiversity of plants: a revolution in the making.

              Ching-Fang Yu, Vincenzo Luca, Vonny Salim … (2012)
              Only a small fraction of the immense diversity of plant metabolism has been explored for the production of new medicines and other products important to human well-being. The availability of inexpensive high-throughput sequencing is rapidly expanding the number of species that can be investigated for the speedy discovery of previously unknown enzymes and pathways. Exploitation of these resources is being carried out through interdisciplinary synthetic and chemical biology to engineer pathways in plant and microbial systems for improving the production of existing medicines and to create libraries of biologically active products that can be screened for new drug applications.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Curr Top Med Chem
                Journal ID (iso-abbrev): Curr Top Med Chem
                Journal ID (publisher-id): CTMC
                Title: Current Topics in Medicinal Chemistry
                Publisher: Bentham Science Publishers
                ISSN (Print): 1568-0266
                ISSN (Electronic): 1873-4294
                Publication date (Electronic): January 2014
                Publication date (Print): January 2014
                Volume: 14
                Pages: 274-289
                Affiliations
                Botanic Garden, Natural History Museum of Denmark, Sølvgade 83, Opg. S, Copenhagen DK-1307, Denmark
                Author notes
                [* ]Address correspondence to this author at the Botanic Garden, Natural History Museum of Denmark, Sølvgade 83, Opg. S, Copenhagen DK-1307, Denmark; Tel: +45-3532 2248;E-mail: sonny.larsson.phd@ 123456gmail.com
                Article
                Publisher ID: CTMC-14-274
                DOI: 10.2174/1568026613666131216110417
                PMC ID: 3884533
                PubMed ID: 24359194
                SO-VID: 809969cf-69b4-4585-9230-c16626c87c9a
                Copyright © © 2013 Bentham Science Publishers
                License:

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                Date received : 29 January 2013
                Date revision received : 28 April 2013
                Date accepted : 25 October 2013
                Categories
                Subject: Article

                ScienceOpen disciplines: Pharmaceutical chemistry
                Keywords: alkaloids,colchicaceae,colchicine,evolution,biosynthetic pathways,phylogenetic prediction.
                Data availability:
                ScienceOpen disciplines: Pharmaceutical chemistry
                Keywords: alkaloids, colchicaceae, colchicine, evolution, biosynthetic pathways, phylogenetic prediction.

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