Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer

As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocycli...

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Detalles Bibliográficos
Autores principales: Feng, Li, Yu, Shujia, Wang, Hai, Yang, Shengwei, Li, Xue, Dai, Hongjuan, Zhao, Liwen, Jiang, Cheng, Wang, Yazhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198214/
https://www.ncbi.nlm.nih.gov/pubmed/34070610
http://dx.doi.org/10.3390/molecules26113162
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author Feng, Li
Yu, Shujia
Wang, Hai
Yang, Shengwei
Li, Xue
Dai, Hongjuan
Zhao, Liwen
Jiang, Cheng
Wang, Yazhou
author_facet Feng, Li
Yu, Shujia
Wang, Hai
Yang, Shengwei
Li, Xue
Dai, Hongjuan
Zhao, Liwen
Jiang, Cheng
Wang, Yazhou
author_sort Feng, Li
collection PubMed
description As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC(50) value of 96 nM. Furthermore, compounds B16–P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.
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spelling pubmed-81982142021-06-14 Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer Feng, Li Yu, Shujia Wang, Hai Yang, Shengwei Li, Xue Dai, Hongjuan Zhao, Liwen Jiang, Cheng Wang, Yazhou Molecules Article As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC(50) value of 96 nM. Furthermore, compounds B16–P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model. MDPI 2021-05-25 /pmc/articles/PMC8198214/ /pubmed/34070610 http://dx.doi.org/10.3390/molecules26113162 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
Feng, Li
Yu, Shujia
Wang, Hai
Yang, Shengwei
Li, Xue
Dai, Hongjuan
Zhao, Liwen
Jiang, Cheng
Wang, Yazhou
Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title_full Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title_fullStr Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title_full_unstemmed Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title_short Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer
title_sort synthesis and biological evaluation of spirocyclic chromane derivatives as a potential treatment of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198214/
https://www.ncbi.nlm.nih.gov/pubmed/34070610
http://dx.doi.org/10.3390/molecules26113162
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