Yingchao Li, Xiaoyu Liu, Farong Lu, Huichao Li, Jiaming Zhang, Yawei Zhang, Wenchao Li, Weiping Wang, Miaomiao Yang, Zhining Ma, Hui Zhang, Xiaomian Zhou, Youjun Xu, Zhonggui He, Jin Sun, Tianhong Zhang, Qikun Jiang
Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'- O -CO- N -isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma...
April 3, 2024: Journal of Agricultural and Food Chemistry