Identification of (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors and the mechanism exploration
Identification of (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors and the mechanism exploration
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新型脲酶抑制剂(N-芳基-N-芳基磺酰基)氨基乙酰异羟肟酸的鉴定及机理探索
DOI：
10.1016/j.bioorg.2022.106275
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发表时间：
2023
影响因子：
5.1
通讯作者：
Hai-Liang Zhu
中科院分区：
文献类型：
--
作者：
Su-Ya Li;Yan Zhang;Yi-Ning Wang;Liang-Chao Yuan;Cui-Cui Kong;Zhu-Ping Xiao;Hai-Liang Zhu
合成了33个N-芳基-N-芳基磺酰基氨基乙酰异羟肟酸类化合物，旨在开发新型脲酶抑制剂。其中2-（N-（3-硝基苯基）-N-（4-叔丁基苯磺酰基））氨基乙酰异羟肟酸（e2）对幽门螺杆菌尿素酶具有很好的抑制活性，对哺乳动物细胞无明显的细胞毒性。化合物2显示出比临床使用的脲酶抑制剂乙酰异羟肟酸高690倍以上的效力，以混合机制可逆地抑制脲酶。分子模拟结果表明，（N-芳基-N-芳基磺酰基）氨基乙酰异羟肟酸可能结合镍离子和两个“Y”形疏水区域。
Thirty-three (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids were synthesized in an effort to develop novel urease inhibitors. Among these compounds, 2-(N-(3-nitrophenyl)-N-(4-tert-butylphenylsulfonyl))aminoacetohydroxamic acid (e2) exhibited excellent inhibitory activity againstHelicobacter pyloriurease with no perceptible cytotoxicity to mammalian cells. Compounde2showed over 690-fold higher potency than the clinical used urease inhibitor acetohydroxamic acid, reversibly inhibiting urease with a mixed mechanism. Molecular modeling revealed that (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids may possibly bind Ni ions and two hydrophobic regions with a 'Y'-like shape.