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Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis
Aminopeptidase N is considered as a promising anti-tumor target due to its role in tumor invasion, metastasis and angiogenesis. In this report, a new series of pyrazoline-based derivatives were designed, synthesized and evaluated for biological activities. The structure–activity relationships of the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034162/ https://www.ncbi.nlm.nih.gov/pubmed/35478833 http://dx.doi.org/10.1039/d1ra03629g |
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author | Cao, Jiangying Zhao, Chunlong Dong, Hang Xu, Qifu Zhang, Yingjie |
author_facet | Cao, Jiangying Zhao, Chunlong Dong, Hang Xu, Qifu Zhang, Yingjie |
author_sort | Cao, Jiangying |
collection | PubMed |
description | Aminopeptidase N is considered as a promising anti-tumor target due to its role in tumor invasion, metastasis and angiogenesis. In this report, a new series of pyrazoline-based derivatives were designed, synthesized and evaluated for biological activities. The structure–activity relationships of these pyrazoline-based derivatives were also discussed in detail. Among them, compound 2k, with 2,6-dichloro substitution, showed the best APN inhibitory activity, of which the IC(50) value was two orders of magnitude lower than that of the positive control bestatin. At the same concentration of 100 μM, the in vitro anti-invasion activity of compound 2k was also significantly better than that of bestatin. Moreover, compound 2k could effectively prevent the pulmonary metastasis of mice H22 hepatoma cells in vivo, supporting its further research and development as an antitumor agent. |
format | Online Article Text |
id | pubmed-9034162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90341622022-04-26 Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis Cao, Jiangying Zhao, Chunlong Dong, Hang Xu, Qifu Zhang, Yingjie RSC Adv Chemistry Aminopeptidase N is considered as a promising anti-tumor target due to its role in tumor invasion, metastasis and angiogenesis. In this report, a new series of pyrazoline-based derivatives were designed, synthesized and evaluated for biological activities. The structure–activity relationships of these pyrazoline-based derivatives were also discussed in detail. Among them, compound 2k, with 2,6-dichloro substitution, showed the best APN inhibitory activity, of which the IC(50) value was two orders of magnitude lower than that of the positive control bestatin. At the same concentration of 100 μM, the in vitro anti-invasion activity of compound 2k was also significantly better than that of bestatin. Moreover, compound 2k could effectively prevent the pulmonary metastasis of mice H22 hepatoma cells in vivo, supporting its further research and development as an antitumor agent. The Royal Society of Chemistry 2021-06-17 /pmc/articles/PMC9034162/ /pubmed/35478833 http://dx.doi.org/10.1039/d1ra03629g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Cao, Jiangying Zhao, Chunlong Dong, Hang Xu, Qifu Zhang, Yingjie Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title | Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title_full | Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title_fullStr | Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title_full_unstemmed | Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title_short | Development of pyrazoline-based derivatives as aminopeptidase N inhibitors to overcome cancer invasion and metastasis |
title_sort | development of pyrazoline-based derivatives as aminopeptidase n inhibitors to overcome cancer invasion and metastasis |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034162/ https://www.ncbi.nlm.nih.gov/pubmed/35478833 http://dx.doi.org/10.1039/d1ra03629g |
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