Identification of (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors and the mechanism exploration

Su-Ya Li; Yan Zhang; Yi-Ning Wang; Liang-Chao Yuan; Cui-Cui Kong; Zhu-Ping Xiao; Hai-Liang Zhu

doi:10.1016/j.bioorg.2022.106275

Identification of (N-aryl-N-arylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors and the mechanism exploration

Bioorg Chem. 2023 Jan:130:106275. doi: 10.1016/j.bioorg.2022.106275. Epub 2022 Nov 14.

Authors

Su-Ya Li¹, Yan Zhang¹, Yi-Ning Wang¹, Liang-Chao Yuan², Cui-Cui Kong¹, Zhu-Ping Xiao³, Hai-Liang Zhu⁴

Affiliations

¹ Hunan Provincial Key Laboratory of Research, Resource Mining and High-valued Utilization on Edible & Medicinal Plant, National Demonstration Center for Experimental Chemistry Education, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
² State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
³ Hunan Provincial Key Laboratory of Research, Resource Mining and High-valued Utilization on Edible & Medicinal Plant, National Demonstration Center for Experimental Chemistry Education, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xiaozhuping2005@163.com.
⁴ Hunan Provincial Key Laboratory of Research, Resource Mining and High-valued Utilization on Edible & Medicinal Plant, National Demonstration Center for Experimental Chemistry Education, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: zhuhl@nju.edu.cn.

PMID: 36410113
DOI: 10.1016/j.bioorg.2022.106275

Abstract

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 against Helicobacter pylori urease with no perceptible cytotoxicity to mammalian cells. Compound e2 showed 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.

Keywords: Arylsulfonamide; Hydroxamic acid; Kinetic study; Molecular docking; Urease inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Helicobacter pylori*
Mammals / metabolism
Models, Molecular
Urease*

Substances

Urease
Enzyme Inhibitors
Anti-Bacterial Agents