Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.

中文翻译：

---

高灵敏羧酸酯酶探针的合理设计及其在高通量筛选中发现羧酸酯酶抑制剂的应用

通过无创动态成像追踪羧酸酯酶（CES）对于诊断和治疗CES相关代谢疾病具有重要意义。在此，设计并合成了三种基于 BODIPY 的荧光探针，其吡啶单元通过乙酰氧基苄基季铵化，用于基于光诱导电子转移过程检测 CES。值得注意的是，在这些探针中，BDPN2-CES 在 10 分钟内对 CES 表现出显着的 182 倍荧光增强。此外，BDPN2-CES 成功实现了活细胞内源性 CES 变化的实时成像。利用BDPN2-CES，建立了CES抑制剂的可视化高通量筛选方法，最终发现了一种来自化学库的高效抑制剂WZU-13。这些发现表明 BDPN2-CES 可以为诊断 CES 相关疾病提供新途径，并且 WZU-13 成为 CES 过度表达病理过程的有前途的治疗候选者。