Sepsis is a life-threatening disease that affects millions of people worldwide. Microbial infections that lead to sepsis syndrome are associated with an increased production of inflammatory molecules. Aldose reductase has recently emerged as a molecular target that is involved in various inflammatory diseases, including sepsis. Herein, a series of previously synthesized benzothiazole-based thiazolidinones that exhibited strong antibacterial and antifungal activities has been evaluated for inhibition efficacy against aldose reductase and selectivity toward aldehyde reductase under in vitro conditions. The most promising inhibitor 5 was characterized with IC₅₀ value of 3.99 μM and a moderate selectivity. Molecular docking simulations revealed the binding mode of compounds at the active site of human aldose reductase. Moreover, owning to the absence of an acidic pharmacophore, good membrane permeation of the novel aldose reductase inhibitors was predicted. Excellent “drug-likeness” was assessed for most of the compounds by applying the criteria of Lipinski’s “rule of five”.

脓毒症是一种危及生命的疾病，影响着全世界数百万人。导致脓毒症综合征的微生物感染与炎症分子的产生增加有关。醛糖还原酶最近已成为涉及各种炎症性疾病（包括败血症）的分子靶标。在此，已经评估了一系列先前合成的具有强抗菌和抗真菌活性的基于苯并噻唑的噻唑烷酮在体外条件下对醛糖还原酶的抑制功效和对醛还原酶的选择性。最有希望的抑制剂 5 以 IC _50为特征值为 3.99 μM，选择性适中。分子对接模拟揭示了化合物在人醛糖还原酶活性位点的结合模式。此外，由于没有酸性药效团，预计新型醛糖还原酶抑制剂具有良好的膜渗透性。通过应用 Lipinski 的“五规则”标准，对大多数化合物进行了出色的“药物相似性”评估。