Kuzu Burak, Yetkin Derya, Hepokur Ceylan, Algul Oztekin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, Türkiye.
Advance Technology Education Research and Application Centre, Mersin University, Mersin, Türkiye.
Chem Biol Drug Des. 2025 Mar;105(3):e70078. doi: 10.1111/cbdd.70078.
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 IC 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.
本研究介绍了一系列新型吡咯连接双苯并恶唑（PTB）衍生物作为靶向MCF-7人乳腺癌细胞系的潜在凋亡诱导剂的设计、合成及生物学评价。使用MTT法在体外评估了这些化合物的抗癌活性，以他莫昔芬作为参考治疗剂。化合物B8、B14和B18对MCF-7细胞表现出显著的细胞毒性，与他莫昔芬相比，其IC值低约8倍，同时对健康成纤维细胞的影响最小。进一步研究表明，这些化合物可有效诱导早期凋亡，并在癌细胞中选择性地将细胞周期阻滞在G1期。基因表达分析证实了MCF-7细胞中caspase-9介导的凋亡途径的选择性激活，为其潜在的分子机制提供了见解。这些发现突出了PTB衍生物作为强效抗癌剂的潜在前景，为开发利用凋亡诱导改善治疗效果的乳腺癌靶向治疗奠定了基础。
