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Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists

Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic acti...

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Autores principales: Qi, Yueheng, Xue, Baoli, Chen, Shijin, Wang, Wang, Zhou, Haifeng, Chen, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671208/
https://www.ncbi.nlm.nih.gov/pubmed/36405317
http://dx.doi.org/10.3389/fchem.2022.1053675
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author Qi, Yueheng
Xue, Baoli
Chen, Shijin
Wang, Wang
Zhou, Haifeng
Chen, Hong
author_facet Qi, Yueheng
Xue, Baoli
Chen, Shijin
Wang, Wang
Zhou, Haifeng
Chen, Hong
author_sort Qi, Yueheng
collection PubMed
description Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic activity of PC-3, LNCaP, DU145 and androgen receptor, it was found that the mono-substituted derivatives on the phenyl group (4, 6, 7, and 9) displayed strong cytotoxic activities, and compounds 11–16 showed relatively strong antagonistic potency against AR (Inhibition% >55). Docking analysis showed that compounds 11 and 12 mainly bind to AR receptor through hydrogen bonds and hydrophobic bonds, and the structure-activity relationship was discussed based on activity data. These results suggested that these compounds may have instructive implications for drug structural modification in prostate cancer.
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spelling pubmed-96712082022-11-18 Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists Qi, Yueheng Xue, Baoli Chen, Shijin Wang, Wang Zhou, Haifeng Chen, Hong Front Chem Chemistry Prostate cancer (PCa) is a malignant tumor with a higher mortality rate in the male reproductive system. In this study, the hydroxyazine derivatives were synthesized with different structure from traditional anti-prostate cancer drugs. In the evaluation of in vitro cytotoxicity and antagonistic activity of PC-3, LNCaP, DU145 and androgen receptor, it was found that the mono-substituted derivatives on the phenyl group (4, 6, 7, and 9) displayed strong cytotoxic activities, and compounds 11–16 showed relatively strong antagonistic potency against AR (Inhibition% >55). Docking analysis showed that compounds 11 and 12 mainly bind to AR receptor through hydrogen bonds and hydrophobic bonds, and the structure-activity relationship was discussed based on activity data. These results suggested that these compounds may have instructive implications for drug structural modification in prostate cancer. Frontiers Media S.A. 2022-11-03 /pmc/articles/PMC9671208/ /pubmed/36405317 http://dx.doi.org/10.3389/fchem.2022.1053675 Text en Copyright © 2022 Qi, Xue, Chen, Wang, Zhou and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Qi, Yueheng
Xue, Baoli
Chen, Shijin
Wang, Wang
Zhou, Haifeng
Chen, Hong
Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title_full Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title_fullStr Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title_full_unstemmed Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title_short Synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential AR antagonists
title_sort synthesis, biological evaluation, and molecular docking of novel hydroxyzine derivatives as potential ar antagonists
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671208/
https://www.ncbi.nlm.nih.gov/pubmed/36405317
http://dx.doi.org/10.3389/fchem.2022.1053675
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