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Bracken (Pteridium aquilinum) is a toxic and yet edible plant which is distributed in many parts of the world. The carcinogenicity of bracken has been a long-standing problem. This review provides an account of the extensive studies on a bracken carcinogen. Development of a new and mild extraction method coupled with a carcinogenicity test for rats as a bioassay led to the discovery and isolation of ptaquiloside; the biological activities of this long-sought carcinogen are described here. The ultimate carcinogen derived from ptaquiloside is so reactive that it not only efficiently alkylates sulfur-containing amino acids and DNA, but also cleaves DNA. The molecular mechanism of this DNA cleavage was determined. Furthermore, both enantiomers as well as artificial analogues of the ultimate carcinogen were synthesized, and their DNA-cleaving activities were evaluated. Related studies on the bracken carcinogen are also briefly described.

structure elucidation, glycosides, Bioorganic chemistry, terpenoids, DNA cleavage

Publication DOI: 10.1002/(sici)1521-3773(19980803)37:13/14<1818::aid-anie1818>3.0.co;2-8
Journal NLM ID: 0370543
Publisher: Weinheim: Wiley-VCH
Correspondence: Yamada K
Institutions: Department of Chemistry, Faculty of Science, Chikusa, Nagoya 464, Japan

Chromatographic fractionation, monitored by brine shrimp bioassay, led to the isolation of the first protoilludane-type sesquiterpene glucoside, pteridanoside (5), from a bioactive hot-water extract of the neotropical bracken fern Pteridium aquilinum var. caudatum (Dennstaedtiaceae). The enzymatic hydrolysis of 5 yielded its aglycon, pteridanone (6), and D- glucose. The absolute stereostructure of 5 was confirmed by the CD spectroscopic analysis of 6. Pteridanoside (5) exhibited toxicity (LC50 of 250 μg/ml at 24 h and 62.5 μg/ml at 48 h) toward brine shrimp, while the aglycon 6 did not.

circular dichroism, biologically active compound, phytotoxinterpene and terpenoid

Publication DOI: 10.1016/S0040-4020(99)00728-0
Journal NLM ID: 2984170R
Publisher: Pergamon Press
Institutions: Department of Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida 5101, Venezuela
Methods: 13C NMR, 1H NMR, IR, FAB-MS, enzymatic hydrolysis, HPLC, UV, molecular modeling, optical rotation measurement, acetylation, CD, molecular mechanics, toxicity assays, HMBC, DEPT, NOESY, conformational analysis, sulfuric acid methanolysis, DFQ-COSY

Our food contains, in addition to the many well-known major (protein, fat, carbohydrate, and fiber) and minor (vitamins, minerals, and nonessential compounds) nutrients, thousands of naturally present toxic plant compounds. Some are known or strongly suspected to cause cancer in laboratory animals and, thus, may be potentially carcinogenic in people. Many of these compounds are commonly termed "nature's pesticides" because they are often toxic to predators, such as insects and animals, thereby conferring a competitive advantage to the plant that produces them. Other natural toxins in plants have no known role. Although these chemicals are in every meal we eat, they have received little attention compared to that given to minute residues of synthetic chemicals such as PCBs and pesticides. Our food contains significantly greater amounts of natural plant toxins and carcinogens than the synthetic kind, and our bodies aren't able to distinguish between the two. Still, while popular notion remains that "natural is good," it is clear that natural toxins pose a far greater health risk than that posed by synthetic chemicals in our foods.

Publication DOI: 10.1201/9781420038316.ch6
Publisher: CRC Press, Inc.
Editors: Helferich W, Winter CK
Institutions: Utah State University, Logan, USA

Consumption of the bracken fern Pteridium aquilinum by cattle has been shown to induce bladder and intestinal carcinomas in cattle and to cause a number of diseases in other farm animals. An unstable glucoside named ptaquiloside, containing a reactive cyclopropane ring, has been isolated from the fern and its potent carcinogenicity proven. Nineteen of 31 ferns tested by chemotaxonomic methods in Japan have been found to contain potentially carcinogenic ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum. Hydrolysis of ptaquilosides leads to pterosins; under milder conditions a dienone which is believed to be the primary carcinogen is obtained. Hypacrone, a sesquiterpine containing a reactive cyclopropane ring, has been isolated from Hypolepis punctata and its structure proved by synthesis. Illudins, structurally similar to ptaquiloside, have been isolated from the basidiomycete Omphalotus illudens. These give anti-tumour activity and similar reactivity with nucleophiles to ptaquiloside. Compound CC-1065, a highly toxic antibiotic also containing a cyclopropane ring, has been isolated from Streptomyces zelensis. The mechanism of its reactivity with DNA has been compared to that of ptaquiloside and the small structural differences between carcinogenic and anti-tumour activity discussed. Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity, have been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA. The reactivity of cysteine with ptaquilosides and illudins is discussed, as is the role of cysteine alkylating agents in apoptosis.

bracken, carcinogenic, ptaquiloside, ferns, illudins

NCBI PubMed ID: 10970694
Publication DOI: 10.1054/bjoc.2000.1368
Journal NLM ID: 0370635
Publisher: London: Nature Publishing Group on behalf of Cancer Research UK
Institutions: Menai Organics Ltd, MENTEC, Bangor, UK, Department of Chemistry, University of Wales, Bangor, UK
Methods: biological assays