Pyrrole-Tethered Bisbenzoxazole Derivatives: Apoptosis-Inducing Agents Targeting Breast Cancer Cells

IF 3.2 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Chemical Biology & Drug Design Pub Date : 2025-03-13 DOI:10.1111/cbdd.70078
Burak Kuzu, Derya Yetkin, Ceylan Hepokur, Oztekin Algul
{"title":"Pyrrole-Tethered Bisbenzoxazole Derivatives: Apoptosis-Inducing Agents Targeting Breast Cancer Cells","authors":"Burak Kuzu,&nbsp;Derya Yetkin,&nbsp;Ceylan Hepokur,&nbsp;Oztekin Algul","doi":"10.1111/cbdd.70078","DOIUrl":null,"url":null,"abstract":"<p>This study presents the design, synthesis, and biological evaluation of a series of novel pyrrole-tethered bisbenzoxazole (PTB) derivatives as potential apoptosis-inducing agents targeting the MCF-7 human breast cancer cell line. The anticancer activity of these compounds was evaluated in vitro using the MTT assay, with tamoxifen serving as the reference therapeutic agent. Compounds <b>B8</b>, <b>B14</b>, and <b>B18</b> demonstrated remarkable cytotoxicity against MCF-7 cells, exhibiting approximately 8-fold lower IC<sub>50</sub> values compared to tamoxifen, while showing minimal effects on healthy fibroblasts. Further investigations revealed that these compounds effectively induced early-stage apoptosis and selectively arrested the cell cycle at the G1 phase in cancer cells. Gene expression analysis confirmed selective activation of the caspase-9-mediated apoptotic pathway in MCF-7 cells, providing insights into their underlying molecular mechanisms. These findings highlight the promising potential of PTB derivatives as potent anticancer agents, laying the groundwork for the development of targeted therapies for breast cancer that leverage apoptosis induction for improved therapeutic outcomes.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70078","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70078","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

Abstract

This study presents the design, synthesis, and biological evaluation of a series of novel pyrrole-tethered bisbenzoxazole (PTB) derivatives as potential apoptosis-inducing agents targeting the MCF-7 human breast cancer cell line. The anticancer activity of these compounds was evaluated in vitro using the MTT assay, with tamoxifen serving as the reference therapeutic agent. Compounds B8, B14, and B18 demonstrated remarkable cytotoxicity against MCF-7 cells, exhibiting approximately 8-fold lower IC50 values compared to tamoxifen, while showing minimal effects on healthy fibroblasts. Further investigations revealed that these compounds effectively induced early-stage apoptosis and selectively arrested the cell cycle at the G1 phase in cancer cells. Gene expression analysis confirmed selective activation of the caspase-9-mediated apoptotic pathway in MCF-7 cells, providing insights into their underlying molecular mechanisms. These findings highlight the promising potential of PTB derivatives as potent anticancer agents, laying the groundwork for the development of targeted therapies for breast cancer that leverage apoptosis induction for improved therapeutic outcomes.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
本研究介绍了一系列新型吡咯系双苯并恶唑(PTB)衍生物的设计、合成和生物学评价,这些衍生物是针对 MCF-7 人类乳腺癌细胞系的潜在凋亡诱导剂。这些化合物的抗癌活性通过 MTT 试验进行了体外评估,并以他莫昔芬作为参照治疗药物。化合物 B8、B14 和 B18 对 MCF-7 细胞具有显著的细胞毒性,其 IC50 值比他莫昔芬低约 8 倍,同时对健康成纤维细胞的影响极小。进一步研究发现,这些化合物能有效诱导癌细胞早期凋亡,并选择性地将细胞周期阻滞在 G1 期。基因表达分析证实,在 MCF-7 细胞中,Caspase-9 介导的凋亡通路被选择性激活,这为了解其潜在的分子机制提供了线索。这些发现凸显了 PTB 衍生物作为强效抗癌剂的巨大潜力,为开发利用凋亡诱导改善治疗效果的乳腺癌靶向疗法奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 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.
期刊最新文献
Pyrrole-Tethered Bisbenzoxazole Derivatives: Apoptosis-Inducing Agents Targeting Breast Cancer Cells Moscatilin Induces Ferroptosis in Clear Cell Renal Cell Carcinoma via the JAK–STAT Signaling Pathway Identification of Potential PBP2a Inhibitors Against Methicillin-Resistant Staphylococcus aureus via Drug Repurposing and Combination Therapy Targeting Blood-Stage Malaria: Design, Synthesis, Characterization, In Vitro, and In Silico Evaluation of Pyrrolidinodiazenyl Chalcones Machine Learning-Based Discovery of a Novel Noncovalent MurA Inhibitor as an Antibacterial Agent
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1