Design, synthesis, and activity evaluation of indole derivatives as potential stabilizers for p53 Y220C
文献类型：期刊论文
| 作者 | Li, Linquan2,3; Gu, Xi5; Meng, Jingyi4,6; Wen, Yiming3,4,5; Yi, Jing2; Xu, Fengqian1,3; Zhang, Li2; Zhang, Sulin4,5; Zuo, Zhili2,3 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2025-06-01 |
| 卷号 | 121页码:9 |
| 关键词 | p53 Y220C Synthesis Structural modification Drug design |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2025.130161 |
| 英文摘要 | The p53 Y220C mutation is frequently observed in human cancers. This mutation renders the p53 Y220C unstable at physiological temperatures, leading to a loss of its normal function and promoting tumor development. In this study, a total of eight compounds were designed and synthesized based on the active compound C8. The protein thermal shift assay revealed that both C8-3b and C8-6 exhibited similar activity of C8, with a Delta Tm value of +0.5 degrees C. Compounds C8-1a, C8-1b, and C8-2b were found to enhance the thermostability of p53 Y220C (Delta Tm: + 1.0 degrees C), the melting temperature exhibits an enhancement of 0.5 degrees C over the C8, indicating that these compounds possess the ability to stabilize p53 Y220C. The results of the cell viability assay revealed that C8-1b exhibited selective inhibitory effects on the proliferation of tumor cells harboring the p53 Y220C mutation. Furthermore, we utilized molecular docking and two-dimensional interaction analysis to elucidate the binding mode and key interactions of these compounds with p53 Y220C. Our study suggests that these compounds could potentially serve as lead compounds for enhancing the stability of p53 Y220C, thus providing a rational approach for designing small molecule stabilizers against p53 mutations. |
| WOS关键词 | MUTATIONS ; RESTORATION ; DATABASE ; RESCUE ; MUTANT |
| 资助项目 | General Program of Applied Basic Research of Yunnan Province[202001AS070026] ; Yunnan Science and Technology Major Project[202202AA100012] ; Youth Innovation Promotion Association CAS[2023296] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001446569900001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316647]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Li; Zhang, Sulin; Zuo, Zhili |
| 作者单位 | 1.Chengdu Med Coll, Coll Pharm, Chengdu 610500, Sichuan, Peoples R China 2.Sichuan Univ Sci & Engn, Sch Chem Engn, Zigong 643000, Peoples R China 3.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Linquan,Gu, Xi,Meng, Jingyi,et al. Design, synthesis, and activity evaluation of indole derivatives as potential stabilizers for p53 Y220C[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2025,121:9. |
| APA | Li, Linquan.,Gu, Xi.,Meng, Jingyi.,Wen, Yiming.,Yi, Jing.,...&Zuo, Zhili.(2025).Design, synthesis, and activity evaluation of indole derivatives as potential stabilizers for p53 Y220C.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,121,9. |
| MLA | Li, Linquan,et al."Design, synthesis, and activity evaluation of indole derivatives as potential stabilizers for p53 Y220C".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 121(2025):9. |
入库方式： OAI收割
来源：上海药物研究所
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