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Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX
A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a K(i) of 0.031 and 7.24 μM,...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230548/ https://www.ncbi.nlm.nih.gov/pubmed/35744849 http://dx.doi.org/10.3390/molecules27123721 |
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author | Wang, Yali Ji, Bo Cheng, Zhongshui Zhang, Lianghui Cheng, Yingying Li, Yingying Ren, Jin Liu, Wenbo Ma, Yuanyuan |
author_facet | Wang, Yali Ji, Bo Cheng, Zhongshui Zhang, Lianghui Cheng, Yingying Li, Yingying Ren, Jin Liu, Wenbo Ma, Yuanyuan |
author_sort | Wang, Yali |
collection | PubMed |
description | A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a K(i) of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC(50) values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation. |
format | Online Article Text |
id | pubmed-9230548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92305482022-06-25 Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX Wang, Yali Ji, Bo Cheng, Zhongshui Zhang, Lianghui Cheng, Yingying Li, Yingying Ren, Jin Liu, Wenbo Ma, Yuanyuan Molecules Article A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a K(i) of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC(50) values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation. MDPI 2022-06-09 /pmc/articles/PMC9230548/ /pubmed/35744849 http://dx.doi.org/10.3390/molecules27123721 Text en © 2022 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 Wang, Yali Ji, Bo Cheng, Zhongshui Zhang, Lianghui Cheng, Yingying Li, Yingying Ren, Jin Liu, Wenbo Ma, Yuanyuan Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title | Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title_full | Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title_fullStr | Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title_full_unstemmed | Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title_short | Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX |
title_sort | synthesis and biological evaluation of novel synthetic indolone derivatives as anti-tumor agents targeting p53-mdm2 and p53-mdmx |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230548/ https://www.ncbi.nlm.nih.gov/pubmed/35744849 http://dx.doi.org/10.3390/molecules27123721 |
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