除了传统的化疗药物外，在癌细胞中差异性过度表达并与其进展相关的关键酶的有效抑制剂通常被认为是治疗癌症的首选药物。醛糖还原酶（AR）主要与糖尿病并发症相关，已知与癌症的发展和耐药性密切相关。 Epalrestat (EPA) 是 FDA 批准的药物，是一种有效的 AR 抑制剂，具有抗癌活性。然而，其较差的药代动力学特性限制了其生物利用度和治疗效果。我们在此报告了酯酶响应性开启荧光前药的第一个例子，用于通过开启荧光读数向癌细胞持续释放 EPA。已知羧酸酯酶在几种器官特异性癌细胞中过度表达，有助于选择性地从前药中释放药物。采用多步有机合成方法合成前药并成功表征。吸收和发射光谱研究表明，在生理条件下，在猪肝酯酶（PLE）的存在下，前药被成功激活。 HPLC 研究揭示了药物和前药中的荧光团随着时间的推移同时释放，并具有机制见解。虽然前药释放的 EPA 对 AR 酶的抑制潜力在水介质中得到了验证，但前药的抗癌活性也在代表性的宫颈癌细胞系中进行了研究。有趣的是，我们的结果表明前药的开发可以显着增强 EPA 的抗癌潜力。最后，通过使用荧光显微镜测量开启荧光，研究了细胞介质中细胞内酯酶从前药释放药物的过程。因此，本研究强调了EPA荧光前药的合理开发，这将有助于增强其抗癌潜力和更好的治疗潜力。

In addition to the conventional chemotherapeutic drugs, potent inhibitors of key enzymes that are differentially overexpressed in cancer cells and associated with its progression are often considered as the drugs of choice for treating cancer. Aldose reductase (AR), which is primarily associated with complications of diabetes, is known to be closely related to the development of cancer and drug resistance. Epalrestat (EPA), an FDA-approved drug, is a potent inhibitor of AR and exhibits anticancer activity. However, its poor pharmacokinetic properties limit its bioavailability and therapeutic benefits. We report herein the first examples of esterase-responsive turn-on fluorogenic prodrugs for the sustained release of EPA to cancer cells with a turn-on fluorescence readout. Carboxylesterases are known to be overexpressed in several organ-specific cancer cells and help in selective uncaging of drug from the prodrugs. The prodrugs were synthesized using a multistep organic synthesis and successfully characterized. Absorption and emission spectroscopic studies indicated successful activation of the prodrugs in the presence of porcine liver esterase (PLE) under physiological condition. HPLC studies revealed a simultaneous release of both the drug and the fluorophore from the prodrugs over time with mechanistic insights. While the inhibitory potential of EPA released from the prodrugs toward the enzyme AR was validated in the aqueous medium, the anticancer activity of the prodrugs was studied in a representative cervical cancer cell line. Interestingly, our results revealed that the development of the prodrugs can significantly enhance the anticancer potential of EPA. Finally, the drug uncaging process from the prodrugs by the intracellular esterases was studied in the cellular medium by measuring the turn-on fluorescence using fluorescence microscopy. Therefore, the present study highlights the rational development of the fluorogenic prodrugs of EPA, which will help enhance its anticancer potential with better therapeutic potential.