{"title":"Design, Synthesis, and Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer","authors":"Shefali Chowdhary, Asif Raza, Natacha Henry, Pascal Roussel, Arun K. Sharma, 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}
引用次数: 0
Abstract
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.
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.