Pharmaceutics (Sep 2021)

Synthesis and Biochemical Evaluation of Baicalein Prodrugs

  • Sang-Hyun Son,
  • Jinhong Kang,
  • Myunghwan Ahn,
  • Soyeon Nam,
  • Yong Woo Jung,
  • Ki Yong Lee,
  • Young Ho Jeon,
  • Youngjoo Byun,
  • Kiho Lee

DOI
https://doi.org/10.3390/pharmaceutics13091516
Journal volume & issue
Vol. 13, no. 9
p. 1516

Abstract

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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.

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