Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs.

中文翻译：

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黄芩素前药的合成及生化评价

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) 是黄芩中的一种类黄酮类似物，具有多种药理活性，包括抗氧化、抗增殖和抗炎活性。我们之前报道过黄芩素抑制胸腺基质淋巴细胞生成素 (TSLP)/TSLP 受体 (TSLPR) 信号通路，可用作治疗哮喘和特应性皮炎的活性成分。然而，黄芩素被迅速代谢为黄芩素和黄芩素-6- O-葡萄糖醛酸在体内，这限制了它的临床前和临床应用。在本研究中，我们设计、合成并评估了黄芩素前药，该前药可通过氨基酸氨基甲酸酯官能团保护黄芩素 A 环 7 位的 OH 基团。综合体外和体内研究确定化合物2作为黄芩素前药候选物，可改善小鼠动物研究中黄芩素的血浆暴露量。我们的结果表明，可以进一步采用这种前药方法来发现口服黄芩素前药。