化学
部分
噻唑
呋喃
大肠杆菌
对接(动物)
立体化学
铅化合物
IC50型
结构-活动关系
组合化学
生物化学
有机化学
体外
医学
基因
护理部
作者
Tao-Shun Zhou,Lu-Lu He,Jing He,Zhikun Yang,Zhen-Yi Zhou,Ao-Qi Du,Jin-Biao Yu,Ya-Sheng Li,Sijia Wang,Bin Wei,Zi-Ning Cui
标识
DOI:10.1016/j.bioorg.2021.105306
摘要
Gut microbial β-glucuronidases have drawn much attention due to their role as a potential therapeutic target to alleviate some drugs or their metabolites-induced gastrointestinal toxicity. In this study, fifteen 5-phenyl-2-furan derivatives containing 1,3-thiazole moiety (1–15) were synthesized and evaluated for their inhibitory effects against Escherichia coli β-glucuronidase (EcGUS). Twelve of them showed satisfactory inhibition against EcGUS with IC50 values ranging from 0.25 μM to 2.13 μM with compound 12 exhibited the best inhibition. Inhibition kinetics studies indicated that compound 12 (Ki = 0.14 ± 0.01 μM) was an uncompetitive inhibitor for EcGUS and molecular docking simulation further predicted the binding model and capability of compound 12 with EcGUS. A preliminary structure-inhibitory activity relationship study revealed that the heterocyclic backbone and bromine substitution of benzene may be essential for inhibition against EcGUS. The compounds have the potential to be applied in drug-induced gastrointestinal toxicity and the findings would help researchers to design and develop more effective 5-phenyl-2-furan type EcGUS inhibitors.
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