Synthesis and biological evaluation of novel 4-Arylaminoquinolines derivatives as EGFR/HDAC inhibitors

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Keke Yao , Yaxin Li , Wei Wei , Sisi Liu , Xiaoli Wang , Jiamin Xu , Ranran Zhang , Zhigang Wu , Chunyan Guo , Leifu Yang , Liming Hu
{"title":"Synthesis and biological evaluation of novel 4-Arylaminoquinolines derivatives as EGFR/HDAC inhibitors","authors":"Keke Yao ,&nbsp;Yaxin Li ,&nbsp;Wei Wei ,&nbsp;Sisi Liu ,&nbsp;Xiaoli Wang ,&nbsp;Jiamin Xu ,&nbsp;Ranran Zhang ,&nbsp;Zhigang Wu ,&nbsp;Chunyan Guo ,&nbsp;Leifu Yang ,&nbsp;Liming Hu","doi":"10.1016/j.bmcl.2025.130214","DOIUrl":null,"url":null,"abstract":"<div><div>Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality worldwide. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the role of epigenetic modifications, such as histone deacetylation, in cancer progression underscore the need for novel therapeutic strategies. This study reports the design, synthesis, and biological evaluation of novel 4-arylaminoquinoline derivatives as dual inhibitors targeting EGFR and histone deacetylase (HDAC). Leveraging structure-activity relationship insights, a series of compounds were synthesized by integrating pharmacophoric elements of EGFR-TKIs and HDAC inhibitors and their kinase and cellular activities were evaluated. Compound <strong>22c2</strong> exhibited the highest inhibitory activities against EGFR (IC<sub>50</sub> = 4.81 nM) and HDAC (IC<sub>50</sub> = 119.4 nM and 354.8 nM for HDAC1 and HDAC3, respectively). Moreover, <strong>22c2</strong> demonstrated excellent anti-proliferative effects on four human cancer cell lines. These findings provide a foundation for developing dual EGFR/HDAC inhibitors as potential anticancer therapeutics.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130214"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X25001234","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality worldwide. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the role of epigenetic modifications, such as histone deacetylation, in cancer progression underscore the need for novel therapeutic strategies. This study reports the design, synthesis, and biological evaluation of novel 4-arylaminoquinoline derivatives as dual inhibitors targeting EGFR and histone deacetylase (HDAC). Leveraging structure-activity relationship insights, a series of compounds were synthesized by integrating pharmacophoric elements of EGFR-TKIs and HDAC inhibitors and their kinase and cellular activities were evaluated. Compound 22c2 exhibited the highest inhibitory activities against EGFR (IC50 = 4.81 nM) and HDAC (IC50 = 119.4 nM and 354.8 nM for HDAC1 and HDAC3, respectively). Moreover, 22c2 demonstrated excellent anti-proliferative effects on four human cancer cell lines. These findings provide a foundation for developing dual EGFR/HDAC inhibitors as potential anticancer therapeutics.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信