Antonio Hernández Daranas

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.

Yessotoxins, a Group of Marine Polyether Toxins: an Overview

Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP) because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA) and dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of protein phosphatases. In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs.

Evaluation of the effects of several zoanthamine-type alkaloids on the aggregation of human platelets.

Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.

New alkaloids from a marine zoanthid

Abstract Five new alkaloids zoanthenol 7,3-hydroxynorzoanthamine 8, 30-hydroxynorzoanthamine 9,11-hydroxynorzoanthamine 10 and 11-hydroxyzoanthamine 11 have been isolated from a marine zoanthid. Their structures were determined through the interpretation of 2D-NMR spectral data. Their relative stereochemistries were proposed on the basis of ROESY data.

Cytotoxic oxasqualenoids from the red alga Laurencia viridis.

Three new polyether squalene derivatives 15-dehydroxythyrsenol A (2), prethyrsenol A (3) and 13-hydroxyprethyrsenol A (4) have been isolated from the red alga Laurencia viridis. Their structures were determined through the interpretation of NMR spectroscopic data and chemical correlations. In addition, four semi-synthetic compounds modulating the solubility of the lead compound dehydrothyrsiferol (1) were prepared without loss of activity. The cytotoxicity of the new compounds exhibited low μM activities. In order to explain their biological properties, docking simulations of the natural and synthetic compounds onto the αvβ3 integrin binding region were carried out.

On the Configuration of Five-Membered Rings: A Spin-Spin Coupling Constant Approach

Five-membered rings are clearly among the most common structural motifs found in chemistry and biology. Nevertheless, the configuration of conformationally mobile five-membered rings is often difficult to assign from nuclear magnetic resonance (NMR) data. A simple, reliable, and efficient approach for the stereochemical analysis of five-membered rings based on the measurement of NMR coupling constants is presented. Density functional theory calculations using representative conformations of the full conformational space available to rings with different substitution patterns were used to identify differences between the accessible coupling constant values for cis and trans relative orientations of the substituents. The calculations were assessed experimentally using NMR data obtained from a number of models. This approach can be easily used to analyze different five-membered rings, such as oxolanes, cyclopentanes, furanosides and pyrrolidines, and their relative configuration can be determined without the need for making further conformational considerations.

Epioxyzoanthamine, a new zoanthamine-type alkaloid and the unusual deuterium exchange in this series

Abstract A new alkaloid, epioxyzoanthamine 4 , has been isolated from a marine zoanthid. Its structure and relative stereochemistry were determined through the interpretation of NMR spectral data. This compound as well as norzoanthamine, showed an unusual deuterium exchange at the methylene C-11 after treatment with D 2 O.

New Polyether Triterpenoids from Laurencia viridis and Their Biological Evaluation

The red seaweed Laurencia viridis is a rich source of secondary metabolites derived from squalene. New polyethers, such as iubol (2), 22-hydroxy-15(28)- dehydrovenustatriol (3), 1,2-dehydropseudodehydrothyrsiferol (4), and secodehydrothyrsiferol (5) have been isolated and characterized from this alga. The structures were determined through the interpretation of NMR spectroscopic data and the relative configuration was proposed on the basis of NOESY spectrum and biogenetic considerations. All new compounds exhibited significant cytotoxic activity against a panel of cancer cell lines.

Marine Macrolides, a Promising Source of Antitumor Compounds

Marine organisms have attracted scientific community as a rich source of natural products with unusual structural features and remarkable biological activities. Marine macrolides are a prominent class of natural products characterized by a highly oxygenated polyene backbone containing a macrocyclic lactone as a conformational constraint. Many marine macrolides possess outstanding cell growth antiproliferative properties, making them valuable molecular probes for the investigation of biochemical pathways and promising lead compounds for the development of new antitumor chemotherapeutic agents. In the present review we intend to focus on marine macrolides with potent cytotoxic activity that could be exploited in cancer research and therapy, along with those macrolides currently in clinical trials and/or preclinical development.

Iron(III) catalyzed direct synthesis of cis-2,7-disubstituted oxepanes. The shortest total synthesis of (+)-isolaurepan.

Prins cyclization of bis-homoallylic alcohols with aldehydes catalyzed by iron(III) salts shows excellent cis selectivity and yields to form 2,7-disubstituted oxepanes. The iron(III) is able to catalyze this process with unactivated olefins. This cyclization was used as the key step in the shortest total synthesis of (+)-isolaurepan.