柚皮素酰腙类衍生物的合成、体外抗氧化活性以及细胞毒性研究

柚皮素作为一种二氢黄酮类化合物，具有抗菌、抗肿瘤、抗氧化等生物活性。但由于柚皮素自身的脂溶性和水溶性都较差，导致其生物利用率不高。因此柚皮素的改性研究受到各界的广泛关注。柚皮素的7位、4′位的酚羟基，以及4位的羰基较为活泼，因此可以通过化学反应修饰柚皮素的结构，改善其水溶性进而改善其生物利用率。据文献报道，酰肼类化合物具有良好的抗氧化活性、抗菌活性、抗癌活性等，但由于酰肼中氨基的影响，对有机体有一定的毒性，因此将酰肼通过改造得到酰腙是改善酰肼毒性的有效手段。Naringenin, as a dihydroflavonoid, possesses antibacterial, anti-tumor, and antioxidant activity. However, the poor lipid and water solubility of naringenin leads to the poor bioavailability. Therefore, naringenin modification has attracted the interest of a lot of scholars. The phenolic hydroxyl groups at positions 7 and 4′ and the carbonyl group at position 4 of naringenin are active. Thus, the structure of naringenin can be modified by chemical reactions to improve the water solubility and further the bioavailability. Hydrazides demonstrate strong antioxidant activity, antibacterial activity, and anti-cancer activity, but they are toxic due to the amino groups. Therefore, the modification of hydrazides to obtain acylhydrazones is an effective means to alleviate the toxicity of hydrazides.

来自西南大学化学化工学院的苏学素及其团队通过在现有关构效关系以及柚皮素改性研究的基础上，在4位引进酰肼基团形成酰腙，期望能得到既有生物活性，又能降低酰肼结构毒性的柚皮素衍生物。结果研究合成得到13种柚皮素的酰腙类衍生物，其中12种未被文献报道。体外抗氧化活性实验表明这13种柚皮素抗氧化活性均强于柚皮素，其中8种衍生物的体外抗氧化活性是柚皮素活性的3到6倍。研究结果为后期的抗氧化食品添加剂及抗氧化药物筛选提供了理论依据。Su Xue-su and his team from College of Chemistry and Chemical Engineering, Southwest University, based on the structure-activity relationship and modification of naringenin, added the hydrazide group at the position 4 to form an acylhydrazone, expecting to obtain naringenin derivatives with both biological activity and reduced toxicity of the hydrazide structure. 13 kinds of naringenin acylhydrazone derivatives were synthesized, 12 of them have not been reported in the literature. The antioxidant activity of 13 compounds is stronger than that of naringenin, and the antioxidant activity of 8 derivatives is 3 to 6 times higher than that of naringenin. The results provide a theoretical basis for the later screening of antioxidant food additives and antioxidant drugs.

相关研究由董家吏，廖岳婷，苏学素等完成，研究结果发表于《天然产物研究与开发》2021年33卷第4期，双语版已上线（http://jtp.cnki.net/bilingual/detail/html/TRCW202104001?view=2）。The related research was completed by Dong Jia-li, Liao Yue-ting, Su Xue-su. Results are published in the 33rd volume, 4th issue of Natural Products Research and Development, 2021. The bilingual version has been launched (http://jtp.cnki.net/bilingual/detail/html/TRCW202104001?view=2).