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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...

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Autores principales: Cao, Jiangying, Zhao, Chunlong, Dong, Hang, Xu, Qifu, Zhang, Yingjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
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.
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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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