L-Amino acid carbamate prodrugs of scutellarin: synthesis, physiochemical property, Caco-2 cell permeability, and in vitro anti-oxidative activity

A series of 4'-l-amino acid carbamate derivatives of scutellarin methyl ester were synthesized. Physiochemical properties evaluation results showed that designed target compounds have higher chemical and enzymatic stability, and aqueous solubility. The permeability (P (app) (AP to BL)) of 4c, 4f, and 4g in Caco-2 cell was 8, 7, and 13 times higher than that of scutellarin, respectively, especially 4g had highest P (app AP to BL) value (1.85 +/- A 0.29 x 10(-6) cm/s) and lowest ER (P (app BL to AP)/P (app) (AP to BL)) value 0.56. In vitro anti-oxidative evaluation results revealed that 4g can protect against H2O2-induced PC12 cells oxidative damage by attenuating the MMP loss and decreasing H2O2-induced ROS production.