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Article

Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX

by
Yali Wang
1,*,
Bo Ji
1,
Zhongshui Cheng
1,
Lianghui Zhang
1,
Yingying Cheng
1,
Yingying Li
1,
Jin Ren
1,
Wenbo Liu
1 and
Yuanyuan Ma
2
1
School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang 332000, China
2
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
*
Author to whom correspondence should be addressed.
Molecules 2022, 27(12), 3721; https://doi.org/10.3390/molecules27123721
Submission received: 16 May 2022 / Revised: 5 June 2022 / Accepted: 8 June 2022 / Published: 9 June 2022
(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation III)
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Abstract

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 Ki of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC50 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.
Keywords: p53-MDM2; p53-MDMX; indolone derivatives; anti-tumor p53-MDM2; p53-MDMX; indolone derivatives; anti-tumor

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MDPI and ACS Style

Wang, Y.; Ji, B.; Cheng, Z.; Zhang, L.; Cheng, Y.; Li, Y.; Ren, J.; Liu, W.; Ma, Y. Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX. Molecules 2022, 27, 3721. https://doi.org/10.3390/molecules27123721

AMA Style

Wang Y, Ji B, Cheng Z, Zhang L, Cheng Y, Li Y, Ren J, Liu W, Ma Y. Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX. Molecules. 2022; 27(12):3721. https://doi.org/10.3390/molecules27123721

Chicago/Turabian Style

Wang, Yali, Bo Ji, Zhongshui Cheng, Lianghui Zhang, Yingying Cheng, Yingying Li, Jin Ren, Wenbo Liu, and Yuanyuan Ma. 2022. "Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX" Molecules 27, no. 12: 3721. https://doi.org/10.3390/molecules27123721

APA Style

Wang, Y., Ji, B., Cheng, Z., Zhang, L., Cheng, Y., Li, Y., Ren, J., Liu, W., & Ma, Y. (2022). Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX. Molecules, 27(12), 3721. https://doi.org/10.3390/molecules27123721

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