Exploring aliphatic sulfonamides as multiclass inhibitors of the carbonic anhydrases from the pathogen bacterium Vibrio cholerae

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL
Niccolò Paoletti, Simone Giovannuzzi, Alessandro Bonardi, Viviana De Luca, Clemente Capasso, Alessio Nocentini, Paola Gratteri, Claudiu T. Supuran
{"title":"Exploring aliphatic sulfonamides as multiclass inhibitors of the carbonic anhydrases from the pathogen bacterium Vibrio cholerae","authors":"Niccolò Paoletti,&nbsp;Simone Giovannuzzi,&nbsp;Alessandro Bonardi,&nbsp;Viviana De Luca,&nbsp;Clemente Capasso,&nbsp;Alessio Nocentini,&nbsp;Paola Gratteri,&nbsp;Claudiu T. Supuran","doi":"10.1002/ardp.202400814","DOIUrl":null,"url":null,"abstract":"<p>This study investigates aliphatic sulfonamide derivatives as inhibitors of the α-, β-, and γ-class carbonic anhydrase (CA) isoforms from <i>Vibrio cholerae</i> (VchCAs). A series of 26 compounds bearing a triazole linker and urea- or ether-based tails were described and evaluated for their inhibitory action using a stopped-flow CO<sub>2</sub> hydrase technique. These inhibitors demonstrated a preferential efficacy against VchCAβ. Specifically, the ureido derivatives showed the highest inhibitory potency with inhibition constants (<i>K</i><sub>I</sub>s) in the submicromolar range (0.67–0.93 µM). Selectivity indices were calculated to assess the selective inhibition of VchCAβ over human CA I and II, as well as other VchCA isozymes. Urea-linked compounds demonstrated a significant 25- to 125-fold selectivity for VchCAβ over hCAs and 14- to 26-fold over other VchCAs. Molecular modeling elucidated the interactions contributing to the efficacy and selectivity of aliphatic sulfonamides as VchCA inhibitors, aligning with and reinforcing the experimental results. The latter suggests that aliphatic sulfonamides could serve as valid targeted therapeutics to treat <i>V. cholerae</i> infections.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400814","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400814","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

This study investigates aliphatic sulfonamide derivatives as inhibitors of the α-, β-, and γ-class carbonic anhydrase (CA) isoforms from Vibrio cholerae (VchCAs). A series of 26 compounds bearing a triazole linker and urea- or ether-based tails were described and evaluated for their inhibitory action using a stopped-flow CO2 hydrase technique. These inhibitors demonstrated a preferential efficacy against VchCAβ. Specifically, the ureido derivatives showed the highest inhibitory potency with inhibition constants (KIs) in the submicromolar range (0.67–0.93 µM). Selectivity indices were calculated to assess the selective inhibition of VchCAβ over human CA I and II, as well as other VchCA isozymes. Urea-linked compounds demonstrated a significant 25- to 125-fold selectivity for VchCAβ over hCAs and 14- to 26-fold over other VchCAs. Molecular modeling elucidated the interactions contributing to the efficacy and selectivity of aliphatic sulfonamides as VchCA inhibitors, aligning with and reinforcing the experimental results. The latter suggests that aliphatic sulfonamides could serve as valid targeted therapeutics to treat V. cholerae infections.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
Archiv der Pharmazie
Archiv der Pharmazie 医学-化学综合
CiteScore
7.90
自引率
5.90%
发文量
176
审稿时长
3.0 months
期刊介绍: Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信