三唑嘧啶- isatin杂合体作为三阴性乳腺癌有希望的候选物的设计、合成和生物学评价

IF 3.6 3区 医学 Q2 CHEMISTRY, MEDICINAL
Shefali Chowdhary, Asif Raza, Natacha Henry, Pascal Roussel, Arun K. Sharma, Vipan Kumar
{"title":"三唑嘧啶- isatin杂合体作为三阴性乳腺癌有希望的候选物的设计、合成和生物学评价","authors":"Shefali Chowdhary,&nbsp;Asif Raza,&nbsp;Natacha Henry,&nbsp;Pascal Roussel,&nbsp;Arun K. Sharma,&nbsp;Vipan Kumar","doi":"10.1002/ardp.70075","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype marked by pronounced intra-tumoral heterogeneity and frequent therapeutic resistance. In this study, we report the design, synthesis, and biological evaluation of a novel series of triazolopyrimidine–isatin hybrids against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Among them, <b>9h</b> emerged as the most promising candidate, exhibiting potent cytotoxic activity against TNBC cell lines. Notably, <b>9h</b> demonstrated 5.7-fold greater potency than tamoxifen and slightly better efficacy than the reference drug cisplatin against MDA-MB-231 cells. Further, <b>9h</b> induced a significant reduction in MDA-MB-231 cell viability through caspase-mediated apoptosis. Preliminary ADMET predictions were also carried out to assess pharmacokinetic properties.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, Synthesis, and Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer\",\"authors\":\"Shefali Chowdhary,&nbsp;Asif Raza,&nbsp;Natacha Henry,&nbsp;Pascal Roussel,&nbsp;Arun K. Sharma,&nbsp;Vipan Kumar\",\"doi\":\"10.1002/ardp.70075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype marked by pronounced intra-tumoral heterogeneity and frequent therapeutic resistance. In this study, we report the design, synthesis, and biological evaluation of a novel series of triazolopyrimidine–isatin hybrids against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Among them, <b>9h</b> emerged as the most promising candidate, exhibiting potent cytotoxic activity against TNBC cell lines. Notably, <b>9h</b> demonstrated 5.7-fold greater potency than tamoxifen and slightly better efficacy than the reference drug cisplatin against MDA-MB-231 cells. Further, <b>9h</b> induced a significant reduction in MDA-MB-231 cell viability through caspase-mediated apoptosis. Preliminary ADMET predictions were also carried out to assess pharmacokinetic properties.</p></div>\",\"PeriodicalId\":128,\"journal\":{\"name\":\"Archiv der Pharmazie\",\"volume\":\"358 8\",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archiv der Pharmazie\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ardp.70075\",\"RegionNum\":3,\"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":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.70075","RegionNum":3,"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

三阴性乳腺癌(TNBC)是一种具有高度侵袭性的亚型,其特点是肿瘤内的异质性和治疗耐药性。在这项研究中,我们报道了一系列新的三唑嘧啶- isatin杂合体的设计、合成和生物学评价,这些杂合体可以对抗TNBC细胞系MDA-MB-231和MDA-MB-468。其中,9h是最有希望的候选药物,对TNBC细胞系表现出强大的细胞毒活性。值得注意的是,9h对MDA-MB-231细胞的效力比他莫昔芬高5.7倍,比参比药物顺铂略好。此外,9h通过caspase介导的凋亡诱导MDA-MB-231细胞活力显著降低。还进行了初步的ADMET预测以评估药代动力学特性。
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 Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer

Design, Synthesis, and Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype marked by pronounced intra-tumoral heterogeneity and frequent therapeutic resistance. In this study, we report the design, synthesis, and biological evaluation of a novel series of triazolopyrimidine–isatin hybrids against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Among them, 9h emerged as the most promising candidate, exhibiting potent cytotoxic activity against TNBC cell lines. Notably, 9h demonstrated 5.7-fold greater potency than tamoxifen and slightly better efficacy than the reference drug cisplatin against MDA-MB-231 cells. Further, 9h induced a significant reduction in MDA-MB-231 cell viability through caspase-mediated apoptosis. Preliminary ADMET predictions were also carried out to assess pharmacokinetic properties.

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
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
×
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