設計與合成類黃酮衍生物及劑型優化

Abstract

類黃酮化合物具有廣效的活性，如抗氧化、抗凝血、抗發炎。但類黃酮之水溶性限制其動物實驗的活性探討。本研究將針對類黃酮A進行結構相同性研究(cluster study)，以細胞模型探討構效關係；為了提升其水溶解度將其製成微脂體劑型，並合成類黃酮A之葡萄糖苷9、硫酸鉀鹽12、磷酸鈉鹽13，及為了增加其穿透血腦屏障能力與甘胺酸甲酯及甘胺酸形成之氨基甲酸酯15b與16。除了進行這些衍生物的細胞活性試，同時也開發HPLC分析方法測試其溶解度及logP值。綜合以上之結果，可提供類黃酮A結構優化方向，以提供其解決腦神經相關疾病之研究。

Flavonoids comprise multiple biological activities, e.g., anti-oxidative, antithrombotic, and anti-inflammatory activities. Some of flavonoids are of low water solubility which limits their development in animal study. In this thesis, the structure-activity relationship (SAR) of flavonoid A would be discussed via a cluster study. To improve its water solubility, liposome suspension of various formulations have been designed and prepared. For its structural modification, the corresponding glucoside 9, potassium sulfate salt 12, and phosphate sodium salt 13 have also been designed and synthesized. Additionally, to promote its BBB permeation, glycine methyl ester and glycine were coupled with it to form the corresponding carbamates 15b and 16. These derivatives were subsequently measured for their log P values and solubility by the HPLC method. Overall, this study provides the direction of future optimization for the studies of CNS diseases.