Structure–Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo

A series
of unsaturated fatty acids in fish oil and their corresponding
ethanolamide metabolites were explored to find active fish oil components
of antiallergic activity in vitro. Ethanolamides of omega-3 fatty
acids (α-linolenic acid, EPA, and DHA) were found to possess
promising antiallergic activity, whereas free fatty acids and ethanolamides
of other fatty acids exhibited no or weak potency. Based on this finding,
structure–activity relationships of DHA-ethanolamide (DHEA)
derivatives were investigated to yield better fatty acid derivatives
with enhanced antiallergic activity in vitro and in vivo. When the
ethanolamide moiety of DHEA was replaced by the substituted sulfonamide
functionality, highly promising potency was provided in vitro. Compound 59 showed improved antiallergic activity in vivo over DHEA.
The results indicate that optimized DHEA derivatives have enhanced
antiallergic activity in vitro and in vivo, and the resulting structures
will be an important basis for further development of bioavailable
derivatives with promising allergy suppressive activity.