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BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistr...

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Autores principales: Cui, Herong, Guo, Wenbo, Zhang, Beibei, Li, Guoping, Li, Tong, Yuan, Yanyan, Zhang, Na, Yang, Yuwei, Feng, Wuwen, Chu, Fuhao, Wang, Shenglan, Xu, Bing, Wang, Penglong, Lei, Haimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720627/
https://www.ncbi.nlm.nih.gov/pubmed/31434286
http://dx.doi.org/10.3390/ijms20164062
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author Cui, Herong
Guo, Wenbo
Zhang, Beibei
Li, Guoping
Li, Tong
Yuan, Yanyan
Zhang, Na
Yang, Yuwei
Feng, Wuwen
Chu, Fuhao
Wang, Shenglan
Xu, Bing
Wang, Penglong
Lei, Haimin
author_facet Cui, Herong
Guo, Wenbo
Zhang, Beibei
Li, Guoping
Li, Tong
Yuan, Yanyan
Zhang, Na
Yang, Yuwei
Feng, Wuwen
Chu, Fuhao
Wang, Shenglan
Xu, Bing
Wang, Penglong
Lei, Haimin
author_sort Cui, Herong
collection PubMed
description There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine–betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs.
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spelling pubmed-67206272019-09-10 BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation Cui, Herong Guo, Wenbo Zhang, Beibei Li, Guoping Li, Tong Yuan, Yanyan Zhang, Na Yang, Yuwei Feng, Wuwen Chu, Fuhao Wang, Shenglan Xu, Bing Wang, Penglong Lei, Haimin Int J Mol Sci Article There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine–betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs. MDPI 2019-08-20 /pmc/articles/PMC6720627/ /pubmed/31434286 http://dx.doi.org/10.3390/ijms20164062 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cui, Herong
Guo, Wenbo
Zhang, Beibei
Li, Guoping
Li, Tong
Yuan, Yanyan
Zhang, Na
Yang, Yuwei
Feng, Wuwen
Chu, Fuhao
Wang, Shenglan
Xu, Bing
Wang, Penglong
Lei, Haimin
BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title_full BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title_fullStr BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title_full_unstemmed BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title_short BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation
title_sort ba-12 inhibits angiogenesis via glutathione metabolism activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720627/
https://www.ncbi.nlm.nih.gov/pubmed/31434286
http://dx.doi.org/10.3390/ijms20164062
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