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.

本研究针对鱼油中的一系列不饱和脂肪酸及其对应的乙醇酰胺（ethanolamide）代谢物展开探索，旨在体外筛选具有抗变应性活性的鱼油活性成分。研究发现，ω-3脂肪酸（α-亚麻酸、二十碳五烯酸（EPA）、二十二碳六烯酸（DHA））的乙醇酰胺类化合物展现出良好的抗变应性活性，而游离脂肪酸及其他脂肪酸的乙醇酰胺类化合物则无活性或活性微弱。基于上述发现，本研究针对二十二碳六烯酸乙醇酰胺（DHA-ethanolamide，简称DHEA）衍生物的构效关系展开研究，以期获得体外及体内抗变应性活性更优的脂肪酸衍生物。当将DHEA的乙醇酰胺官能团替换为取代磺酰胺（substituted sulfonamide）官能团时，该类衍生物在体外展现出极具潜力的活性。化合物59在体内的抗变应性活性优于DHEA。研究结果表明，优化后的DHEA衍生物在体外及体内的抗变应性活性均得到提升，所得结构将为开发具有良好过敏抑制活性的生物可利用性衍生物提供重要基础。