新型三唑-吲哚衍生物作为有效的可溶性环氧水解酶抑制剂,具有良好的抗癌活性

IF 3.3 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Vijaykumar D. Nimbarte, Shreya S. Sonak, Sharda A. Ishwarkar, Bharat Rathod, Saiprem Nehlani
{"title":"新型三唑-吲哚衍生物作为有效的可溶性环氧水解酶抑制剂,具有良好的抗癌活性","authors":"Vijaykumar D. Nimbarte,&nbsp;Shreya S. Sonak,&nbsp;Sharda A. Ishwarkar,&nbsp;Bharat Rathod,&nbsp;Saiprem Nehlani","doi":"10.1111/cbdd.70164","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.</p>\n </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel Triazole-Linked Indole Derivatives as Potent Soluble Epoxy Hydrolase Inhibitors With Promising Anticancer Activity\",\"authors\":\"Vijaykumar D. Nimbarte,&nbsp;Shreya S. Sonak,&nbsp;Sharda A. Ishwarkar,&nbsp;Bharat Rathod,&nbsp;Saiprem Nehlani\",\"doi\":\"10.1111/cbdd.70164\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.</p>\\n </div>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":\"106 3\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70164\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70164","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

设计、合成了一系列新的三唑-吲哚衍生物,并对其作为可溶性环氧化物水解酶抑制剂(sEHIs)的潜在抗癌活性进行了评价。这些化合物在sEH的疏水口袋内表现出很强的结合亲和力,化合物9a和9b成为最有效的抑制剂,在体外分别实现IC₅0值为0.270±0.014 nM和0.358±0.03 nM。此外,这两种化合物对HeLa细胞都显示出显著的细胞毒活性,IC₅₀值分别为5.366±0.91 μM和5.686±0.73 μM。利用1ZD5晶体结构进行分子对接研究,揭示了与12-(3-金刚烷-1-酰基脲基)-十二烷酸(AUDA)类似的关键氢键相互作用,为其抑制活性提供了机制见解。构效关系(SAR)分析进一步为这些衍生物的合理优化提供了依据。总的来说,这些发现强调了三唑连接的吲哚衍生物是发展seh靶向抗癌治疗的有希望的主要候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Triazole-Linked Indole Derivatives as Potent Soluble Epoxy Hydrolase Inhibitors With Promising Anticancer Activity

A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
×
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:604180095
Book学术官方微信