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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6720627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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