A strategy by integrating biological imaging into early stages of the drug discovery process can improve our understanding of drug activity during preclinical and clinical study. In this article, we designed and synthesized coumarin-based nonsteroidal type fluorescence ligands for drug-target binding imaging. Among these synthesized compounds, 3e, 3f and 3h showed potent ER binding affinity and 3e (IC₅₀ = 0.012 μM) exhibited excellent ERα antagonistic activity, its antiproliferative potency in breast cancer MCF-7 cells is equipotent to the approved drug tamoxifen. The fluorescence of compounds 3e and 3f depended on the solvent properties and showed significant changes when mixed with ERα or ERβ in vitro. Furthermore, target molecule 3e could cross the cell membrane, localize and image drug-target interaction in real time without cell washing. Thus, the coumarin-based platform represents a promising new ER-targeted delivery vehicle with potential imaging and therapeutic properties.

通过将生物成像整合到药物发现过程的早期阶段的策略可以提高我们在临床前和临床研究期间对药物活性的理解。在本文中，我们设计并合成了基于香豆素的非甾体类荧光配体，用于药物靶标结合成像。在这些合成的化合物中，3e、3f和3h显示出有效的 ER 结合亲和力，3e (IC ₅₀  = 0.012 μM) 表现出优异的 ER α拮抗活性，其在乳腺癌 MCF-7 细胞中的抗增殖效力与批准的药物他莫昔芬相当。化合物3e和3f的荧光取决于溶剂性质，在体外与 ER α或 ER β混合时表现出显着变化。此外，靶分子3e可以穿过细胞膜，实时定位和成像药物-靶标相互作用，无需细胞清洗。因此，基于香豆素的平台代表了一种具有潜在成像和治疗特性的有前途的新型 ER 靶向递送载体。