Structure-Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo
Structure-Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo
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DOI：
10.1021/acs.jmedchem.9b00994
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发表时间：
2019-11-14
影响因子：
7.3
通讯作者：
Nishi，Kosuke
中科院分区：
文献类型：
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作者：
Kim，In-Hae;Kanayama，Yoshiki;Nishi，Kosuke
对鱼油中的一系列不饱和脂肪酸及其相应的乙醇酰胺代谢物进行探索，寻找具有体外抗过敏活性的鱼油活性成分。研究发现 omega-3 脂肪酸（α-亚麻酸、EPA 和 DHA）的乙醇酰胺具有良好的抗过敏活性，而游离脂肪酸和其他脂肪酸的乙醇酰胺则没有或很弱的效力。基于这一发现，我们研究了 DHA-乙醇酰胺 (DHEA) 衍生物的结构-活性关系，以产生更好的脂肪酸衍生物，在体外和体内具有增强的抗过敏活性。当 DHEA 的乙醇酰胺部分被取代的磺酰胺官能团取代时，在体外提供了非常有前景的效力。与DHEA相比，化合物59显示出改善的体内抗过敏活性。结果表明，优化的DHEA衍生物具有增强的体外和体内抗过敏活性，所得结构将为进一步开发具有良好的过敏抑制活性的生物可利用衍生物提供重要基础。
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. Compound59showed 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.