Study on the synthesis, physicochemical properties and transdermal absorption of scutellarein prodrugs

In this research, we aimed to improve the lipid solubility and transdermal absorbability of scutellarein through a prodrug strategy, and then improve its efficacy for treating psoriasis. Firstly, we designed and synthesized 19 prodrugs of scutellarein, including AC (alkylcarbonyl), AAC (alkylaminocarbonyl) and AOC (alkyloxycarbonyl) series. Then, we selected three prodrugs (AC-4, AAC-2 and AOC-SEC-4) with proper log P and favorable solubility for subsequent transdermal absorption study, and the results demonstrated the three prodrugs significantly improved the transdermal flux and the drug retention in the skin. Finally, compared with the parent drug, three prodrugs obviously relieved the dorsal lesions of mice with psoriasis, remarkably reduced the epidermal thickening and Ki67 positive cells. Therefore, this study successfully improved the poor transdermal absorbability of scutellarein, dramatically increased its efficacy in treating psoriasis, and provided candidate compounds for the psoriasis treatment.