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（CAs）是金属酶，负责将二氧化碳可逆地水合为碳酸氢根，这是涉及各种生理和病理过程的基本反应。在过去的几十年中，CA被认为是青光眼，癫痫和癌症等不同病理的重要药物靶标。设计有效和选择性抑制剂一直是导致发现新药的杰出目标。在迄今为止开发的不同策略中，基于碳水化合物的CA抑制剂（CAI）的设计已成为一种通用工具，可以选择性地靶向CA。在磺酰胺，次磺酰胺，氨基磺酸盐或香豆素支架中插入糖基部分作为亲水尾基，可以发现许多不同系列的糖基CAI，并具有相关的抑制结果。