Gut microbial β-glucuronidases have the ability to deconjugate glucuronides of some drugs, thus have been considered as an important drug target to alleviate the drug metabolites-induced gastrointestinal toxicity. In this study, thiazolidin-2-cyanamide derivatives containing 5-phenyl-2-furan moiety (1–13) were evaluated for inhibitory activity against Escherichia coli β-glucuronidase (EcGUS). All of them showed more potent inhibition than a commonly used positive control, d-saccharic acid 1,4-lactone, with the IC₅₀ values ranging from 1.2 µM to 23.1 µM. Inhibition kinetics studies indicated that compound 1–3 were competitive type inhibitors for EcGUS. Molecular docking studies were performed and predicted the potential molecular determinants for their potent inhibitory effects towards EcGUS. Structure–inhibitory activity relationship study revealed that chloro substitution on the phenyl moiety was essential for EcGUS inhibition, which would help researchers to design and develop more effective thiazolidin-2-cyanamide type inhibitors against EcGUS.

肠道微生物β-葡糖醛酸糖苷酶具有使某些药物的葡糖醛酸苷结合的能力，因此被认为是减轻药物代谢物引起的胃肠道毒性的重要药物靶标。在这项研究中，评估了含有5-苯基-2-呋喃部分（1-13）的噻唑烷二-2-氰酰胺衍生物对大肠杆菌β-葡萄糖醛酸苷酶（EcGUS）的抑制活性。与常用的阳性对照d-蔗糖1,4-内酯相比，所有化合物均显示出更强的抑制作用，IC ₅₀值范围为1.2 µM至23.1 µM。抑制动力学研究表明，化合物1 - 3是EcGUS的竞争型抑制剂。进行了分子对接研究，并预测了其潜在对EcGUS抑制作用的分子决定因素。结构抑制活性关系研究表明，苯基部分上的氯取代对于EcGUS抑制至关重要，这将有助于研究人员设计和开发更有效的针对EcGUS的噻唑烷二-2-氰酰胺类抑制剂。