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碳水化合物衍生碳酸酐酶抑制剂概述。

An overview of carbohydrate-based carbonic anhydrase inhibitors.

机构信息

Department of Pharmacy, University of Pisa, Pisa, Italy.

出版信息

J Enzyme Inhib Med Chem. 2020 Dec;35(1):1906-1922. doi: 10.1080/14756366.2020.1825409. Epub 2020 Oct 20.

Abstract

Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various physiological and pathological processes. In the last decades, CAs have been considered as important drug targets for different pathologies such as glaucoma, epilepsy and cancer. The design of potent and selective inhibitors has been an outstanding goal leading to the discovery of new drugs. Among the different strategies developed to date, the design of carbohydrate-based CA inhibitors (CAIs) has emerged as a versatile tool in order to selectively target CAs. The insertion of a glycosyl moiety as a hydrophilic tail in sulfonamide, sulfenamide, sulfamate or coumarin scaffolds allowed the discovery of many different series of sugar-based CAIs, with relevant inhibitory results. This review will focus on carbohydrate-based CAIs developed so far, classifying them in glycosidic and glycoconjugated inhibitors based on the conjugation chemistry adopted.

摘要

碳酸酐酶(CA)是一类金属酶,负责将二氧化碳可逆水合为碳酸氢根,这是参与各种生理和病理过程的基本反应。在过去的几十年中,CA 已被认为是治疗青光眼、癫痫和癌症等多种疾病的重要药物靶点。设计高效且选择性的抑制剂一直是一个突出的目标,这导致了新药的发现。在迄今为止开发的各种策略中,基于碳水化合物的 CA 抑制剂(CAI)的设计已成为一种多功能工具,可用于选择性靶向 CA。将糖基部分作为亲水尾巴插入磺酰胺、亚磺酰胺、磺酸盐或香豆素支架中,允许发现许多具有相关抑制效果的不同系列基于糖的 CAI。本综述将重点介绍迄今为止开发的基于碳水化合物的 CAI,根据所采用的缀合化学将它们分类为糖苷和糖缀合物抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ee7/7717713/0547e04d5346/IENZ_A_1825409_F0001_C.jpg

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