三唑系链双萘酰亚胺- isatin杂合体对三阴性乳腺癌和前列腺癌的设计、合成、抗增殖和凋亡评估。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-07-28 DOI:10.1002/cmdc.202500415
Preeti, Asif Raza, Garima Arora, Amit Anand, Arun K. Sharma, Vipan Kumar
{"title":"三唑系链双萘酰亚胺- isatin杂合体对三阴性乳腺癌和前列腺癌的设计、合成、抗增殖和凋亡评估。","authors":"Preeti,&nbsp;Asif Raza,&nbsp;Garima Arora,&nbsp;Amit Anand,&nbsp;Arun K. Sharma,&nbsp;Vipan Kumar","doi":"10.1002/cmdc.202500415","DOIUrl":null,"url":null,"abstract":"<p>This study reports the design, synthesis, and biological evaluation of 1H-1,2,3-triazole-tethered bisnaphthalimide-isatin hybrids as potential antiproliferative agents. The compounds are efficiently synthesized via copper-promoted azide–alkyne cycloaddition and assayed against triple-negative breast (MDA-MB-231) and prostate (DU-145) cancer cell lines. Structure–activity relationship studies reveal that halogen substitution and spacer length substantially influenced anticancer activity. The bisnaphthalimide-isatin hybrid featuring dibromo substitution and a propyl linker demonstrates IC<sub>50</sub> values of 3.3 ± 0.1 μM (DU-145) and 4.4 ± 0.3 μM (MDA-MB-231), comparable to clinical drugs cisplatin and 5-fluorouracil. Notably, it exhibits favorable selectivity indices (2.07–2.76) against cancer versus normal keratinocytes (HaCaT). Mechanistic investigations establish that it induces caspase-mediated apoptosis and molecular docking studies confirmed its strong interaction with DNA topoisomerase II (docking score: −4.894), comparable to doxorubicin.</p>","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 17","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers\",\"authors\":\"Preeti,&nbsp;Asif Raza,&nbsp;Garima Arora,&nbsp;Amit Anand,&nbsp;Arun K. Sharma,&nbsp;Vipan Kumar\",\"doi\":\"10.1002/cmdc.202500415\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>This study reports the design, synthesis, and biological evaluation of 1H-1,2,3-triazole-tethered bisnaphthalimide-isatin hybrids as potential antiproliferative agents. The compounds are efficiently synthesized via copper-promoted azide–alkyne cycloaddition and assayed against triple-negative breast (MDA-MB-231) and prostate (DU-145) cancer cell lines. Structure–activity relationship studies reveal that halogen substitution and spacer length substantially influenced anticancer activity. The bisnaphthalimide-isatin hybrid featuring dibromo substitution and a propyl linker demonstrates IC<sub>50</sub> values of 3.3 ± 0.1 μM (DU-145) and 4.4 ± 0.3 μM (MDA-MB-231), comparable to clinical drugs cisplatin and 5-fluorouracil. Notably, it exhibits favorable selectivity indices (2.07–2.76) against cancer versus normal keratinocytes (HaCaT). Mechanistic investigations establish that it induces caspase-mediated apoptosis and molecular docking studies confirmed its strong interaction with DNA topoisomerase II (docking score: −4.894), comparable to doxorubicin.</p>\",\"PeriodicalId\":147,\"journal\":{\"name\":\"ChemMedChem\",\"volume\":\"20 17\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ChemMedChem\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202500415\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemMedChem","FirstCategoryId":"3","ListUrlMain":"https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202500415","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

本研究报道了1h -1,2,3-三唑系链双萘酰亚胺-isatin杂合体作为潜在的抗增殖剂的设计、合成和生物学评价。这些化合物是通过铜促进叠氮-炔环加成有效合成的,并对三阴性乳腺癌(MDA-MB-231)和前列腺(DU-145)细胞系进行了检测。构效关系研究表明,卤素取代和间隔长度对抗癌活性有显著影响。采用二溴取代和丙基连接的双萘酰亚胺-isatin复合物的IC50值分别为3.3±0.1 μM (DU-145)和4.4±0.3 μM (MDA-MB-231),与临床药物顺铂和5-氟尿嘧啶相当。值得注意的是,它对癌症的选择性指数(2.07-2.76)优于正常角化细胞(HaCaT)。机制研究证实其诱导caspase介导的细胞凋亡,分子对接研究证实其与DNA拓扑异构酶II的强相互作用(对接评分:-4.894),与阿霉素相当。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers

Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers

Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers

Design, Synthesis, and Antiproliferative and Apoptotic Assessment of Triazole-Tethered Bisnaphthalimide-Isatin Hybrids on Triple-Negative Breast and Prostate Cancers

This study reports the design, synthesis, and biological evaluation of 1H-1,2,3-triazole-tethered bisnaphthalimide-isatin hybrids as potential antiproliferative agents. The compounds are efficiently synthesized via copper-promoted azide–alkyne cycloaddition and assayed against triple-negative breast (MDA-MB-231) and prostate (DU-145) cancer cell lines. Structure–activity relationship studies reveal that halogen substitution and spacer length substantially influenced anticancer activity. The bisnaphthalimide-isatin hybrid featuring dibromo substitution and a propyl linker demonstrates IC50 values of 3.3 ± 0.1 μM (DU-145) and 4.4 ± 0.3 μM (MDA-MB-231), comparable to clinical drugs cisplatin and 5-fluorouracil. Notably, it exhibits favorable selectivity indices (2.07–2.76) against cancer versus normal keratinocytes (HaCaT). Mechanistic investigations establish that it induces caspase-mediated apoptosis and molecular docking studies confirmed its strong interaction with DNA topoisomerase II (docking score: −4.894), comparable to doxorubicin.

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
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
×
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