Brevenal / Silurian - LARVOL DELTA

Deciphering the Neurotoxic Effects of Karenia selliformis. (PubMed, Toxins (Basel)) - "While K. selliformis is traditionally linked to neurotoxins like gymnodimines (GYMs), analysis of the strain CREAN-KS02 from Chile's Aysén Region (43° S) revealed no presence of toxins associated with this genus, such as gymnodimines, brevetoxins, or brevenal...Electrophysiological recordings on cultured mouse hippocampal neurons showed that the extract increased cell excitability in a dose-dependent manner, modulating action potential firing and exhibiting an opposed effect to tetrodotoxin. These findings indicate the presence of excitatory neurotoxic compounds affecting mammalian cells. This study provides the first mechanistic evidence of K. selliformis toxicity and highlights potential risks associated with its proliferation in marine environments."

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Brevetoxin versus Brevenal Modulation of Human Nav1 Channels. (PubMed, Mar Drugs) - "Our results are consistent with competitive antagonism between brevetoxins and brevenal, setting a basis for future mutational analyses of Nav channels' interaction with brevetoxins and brevenal. Our findings provide valuable insights into the functional modulation of Nav channels by brevetoxins and brevenal, which may have implications for the development of new Nav channel modulators with potential therapeutic applications."

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Application of a Cholesterol-Based Stationary Phase for the Analysis of Brevetoxins. (PubMed, J Sep Sci) - "A separate protocol was developed for the compounds brevenal and brevenol, also produced by the same algae that make brevetoxins...Brevenal is a natural product under investigation as a therapy for chronic respiratory diseases, such as cystic fibrosis or asthma. The goal of this study was to provide a protocol for the analysis of these compounds that could be further developed into a validated method depending on a particular laboratory's capabilities and to highlight some of the unique features of the cholesterol stationary phase."

Journal • Asthma • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Chemodiversity of Brevetoxins and Other Potentially Toxic Metabolites Produced by Karenia spp. and Their Metabolic Products in Marine Organisms. (PubMed, Mar Drugs) - "also produce brevenal, brevisamide and metabolites belonging to the hemi-brevetoxin, brevisin, tamulamide, gymnocin, gymnodimine, brevisulcenal and brevisulcatic acid groups...New metabolites have yet to be fully described, especially the groups of metabolites discovered in the last two decades (e.g tamulamides). Lastly, this work clarifies the different nomenclatures used in the literature and should help to harmonize practices in the future."

Journal • Review • Metabolic Disorders

Mucus Release and Airway Constriction by TMEM16A May Worsen Pathology in Inflammatory Lung Disease. (PubMed, Int J Mol Sci) - "Activation or potentiation of TMEM16A by the compounds Eact or brevenal, respectively, induced acute mucus release from airway goblet cells and induced bronchoconstriction in mice in vivo. In contrast, niclosamide, an inhibitor of TMEM16A, blocked mucus production and mucus secretion in vivo and in vitro...Activation of TMEM16A in people with inflammatory airway diseases is likely to induce mucus secretion along with airway constriction. In contrast, inhibitors of TMEM16A may suppress pulmonary Th2 inflammation, goblet cell metaplasia, mucus production, and bronchoconstriction, partially by inhibiting expression of SPDEF."

Journal • Asthma • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • SPDEF

Profiling of Brevetoxin Metabolites Produced by Karenia brevis 165 Based on Liquid Chromatography-Mass Spectrometry. (PubMed, Toxins (Basel)) - "Brevenal, a toxic BTX metabolite antagonist, was found for the first time in the culture media...There were significant differences in the types and contents of toxic BTX metabolites with varying growth stages. Therefore, when harmful algal blooms occur, the accurate determination of BTX metabolite types and concentrations will be helpful to assess the ecological disaster risk in order to avoid hazards and provide appropriate disaster warnings."

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Unraveling the Karenia selliformis complex with the description of a non-gymnodimine producing Patagonian phylotype. (PubMed, Harmful Algae) - "However, both CREAN_KS01 and CREAN_KS02 contained two compounds with the same mass transition as brevenal, a brevetoxin related compound...In conclusion, the present study provides evidence for significant genetic and phenotypic variability among worldwide isolates, which points to the existence of a K. selliformis "species complex". The massive fauna mortality during K. selliformis bloom events in the Chilean coast cannot be explained by GYMs nor brevetoxins, but can to a large extent be accounted for by the high production of long-chain PUFAs and/or still uncharacterized highly toxic compounds."

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Endo-selective Epoxide-opening Cascade for Fast Assembly of the Polycyclic Core Structure of Marine Ladder Polyethers. (PubMed, Angew Chem Int Ed Engl) - "Starting from readily accessible homochiral polyepoxy alcohols with a methyl group at all the endo -cyclization sites, we were able to construct polyethers up to five consecutive fused 6-, 7-, and/or 8-membered rings in one step. Notably, molecules with the 7/7/6/6 and 7/7/6/7/6 polyether frameworks of hemibrevetoxin B and brevenal, respectively, could be synthesized in 40% and 17% chemical yields."

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