Azaspiracid substituent at C1 is relevant to in vitro toxicity.

Chemical Research in Toxicology
Natalia VilariñoLuis M Botana

Abstract

The azaspiracids are a group of marine toxins recently described that currently includes 20 analogues. Not much is known about their mechanism of action, although effects on some cellular functions have been found in vitro. We used the reported effects on cell viability, actin cytoskeleton, and caspase activation to study the structure-activity relationship of AZA-1 and AZA-2 and the role of the carboxylic acid moiety in toxicity. AZA-1, AZA-2, and the synthetic AZA-2-methyl ester (AZA-2-ME), where the C1 carboxylic acid moiety of AZA-2 was esterified to the corresponding methyl ester moiety, induced a reduction of cell viability in neuroblastoma and hepatocyte cell lines with similar potency and kinetics. Interestingly, the mast cell line HMC-1 was resistant to AZA-induced cytotoxicity. Actin cytoskeleton alterations and caspase activation appeared after treatment with AZA-1, AZA-2, AZA-2-ME, and biotin-AZA-2 (AZA-2 labeled with biotin at C1) in neuroblastoma cells with similar qualitative, quantitative, and kinetics characteristics. Irreversibility of AZA effects on the actin cytoskeleton and cell morphology after short incubations with the toxin were common to AZA-1, AZA-2, and AZA-2-ME; however, 10-fold higher concentration...Continue Reading

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Citations

Aug 4, 2012·Chemical Research in Toxicology·Michael J TwinerMichael C Sanguinetti
Jan 6, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zhengyu CaoThomas F Murray
Mar 9, 2010·Toxicon : Official Journal of the International Society on Toxinology·M Carmen LouzaoLuis M Botana
Nov 20, 2008·The FEBS Journal·Natalia Vilariño
Feb 13, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sara F FerreiroLuis M Botana
Dec 3, 2014·Toxicon : Official Journal of the International Society on Toxinology·Daniel O'DriscollKevin J James
Sep 1, 2016·Toxicon : Official Journal of the International Society on Toxinology·Barbara DoerrFrank van Pelt
Oct 7, 2016·Archives of Toxicology·Sara F FerreiroLuis M Botana
Oct 20, 2010·Chemical Research in Toxicology·Carolina B WandscheerLuis M Botana

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