Elizabeth M. Mudge , Alistair L. Wilkins , J. Sam Murray , Frode Rise , Christopher O. Miles
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引用次数: 0
Abstract
Gambierones are sulfated polyethers produced by benthic dinoflagellates in the genera Gambierdiscus, Coolia and Fukuyoa. While relative toxicity data for gambierones suggests they are low compared with ciguatoxin analogues, gambierones have been suggested for use as marker compounds for environmental monitoring programs for the presence of Gambierdiscus in marine waters. The published structure of gambierone and analogues of it, including 44-methylgambierone (44-MeGAM), have been reported to possess 1,2- and 4,5-cis diols, while only the 1,2- diol unit has been shown to undergo periodate oxidation. An in-depth analysis of previously reported NMR data for 44-MeGAM in CD3OD showed that the C-4 stereochemistry of 44-MeGAM and other gamberiones was mis-assigned, that the 4-CH2-CHOH-CH2OH and OH groups are equatorially and axially oriented, respectively, rather than vice versa as previously reported. This re-examination of existing 44-MeGAM NMR data also showed that its C-12 and C-13 assignments (and those for other gambierones) should be reversed. In an effort to better understand the C-4 stereochemical and periodate reaction characteristics of gambierones (C-4 is an epimerizable hemiacetal carbon), additional NMR data was acquired in D6-DMSO. Unexpectedly, progressive conversion of 44-MeGAM to a long-term stable ring-A furanoid analogue was observed. A subsequent series of microscale stability trials identified several solvents that affected the solution-stability of 44-MeGAM, and these findings should be taken into consideration during isolation, handling, storage and bioassay evaluations of gambierones in future studies.
期刊介绍:
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.