Cargando…
Synthesis and Biochemical Evaluation of Baicalein Prodrugs
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 lym...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472512/ https://www.ncbi.nlm.nih.gov/pubmed/34575592 http://dx.doi.org/10.3390/pharmaceutics13091516 |
_version_ | 1784574748219408384 |
---|---|
author | Son, Sang-Hyun Kang, Jinhong Ahn, Myunghwan Nam, Soyeon Jung, Yong Woo Lee, Ki Yong Jeon, Young Ho Byun, Youngjoo Lee, Kiho |
author_facet | Son, Sang-Hyun Kang, Jinhong Ahn, Myunghwan Nam, Soyeon Jung, Yong Woo Lee, Ki Yong Jeon, Young Ho Byun, Youngjoo Lee, Kiho |
author_sort | Son, Sang-Hyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8472512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84725122021-09-28 Synthesis and Biochemical Evaluation of Baicalein Prodrugs Son, Sang-Hyun Kang, Jinhong Ahn, Myunghwan Nam, Soyeon Jung, Yong Woo Lee, Ki Yong Jeon, Young Ho Byun, Youngjoo Lee, Kiho Pharmaceutics Article 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. MDPI 2021-09-19 /pmc/articles/PMC8472512/ /pubmed/34575592 http://dx.doi.org/10.3390/pharmaceutics13091516 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Son, Sang-Hyun Kang, Jinhong Ahn, Myunghwan Nam, Soyeon Jung, Yong Woo Lee, Ki Yong Jeon, Young Ho Byun, Youngjoo Lee, Kiho Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title | Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title_full | Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title_fullStr | Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title_full_unstemmed | Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title_short | Synthesis and Biochemical Evaluation of Baicalein Prodrugs |
title_sort | synthesis and biochemical evaluation of baicalein prodrugs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472512/ https://www.ncbi.nlm.nih.gov/pubmed/34575592 http://dx.doi.org/10.3390/pharmaceutics13091516 |
work_keys_str_mv | AT sonsanghyun synthesisandbiochemicalevaluationofbaicaleinprodrugs AT kangjinhong synthesisandbiochemicalevaluationofbaicaleinprodrugs AT ahnmyunghwan synthesisandbiochemicalevaluationofbaicaleinprodrugs AT namsoyeon synthesisandbiochemicalevaluationofbaicaleinprodrugs AT jungyongwoo synthesisandbiochemicalevaluationofbaicaleinprodrugs AT leekiyong synthesisandbiochemicalevaluationofbaicaleinprodrugs AT jeonyoungho synthesisandbiochemicalevaluationofbaicaleinprodrugs AT byunyoungjoo synthesisandbiochemicalevaluationofbaicaleinprodrugs AT leekiho synthesisandbiochemicalevaluationofbaicaleinprodrugs |