Cuffaro Doretta, Nuti Elisa, D'Andrea Felicia, Rossello Armando
Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy.
Pharmaceuticals (Basel). 2020 Nov 10;13(11):376. doi: 10.3390/ph13110376.
Matrix metalloproteinases (MMPs) and A disintegrin and Metalloproteinase (ADAMs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. Upregulation of metzincin activity is a major feature in many serious pathologies such as cancer, inflammations, and infections. In the last decades, many classes of small molecules have been developed directed to inhibit these enzymes. The principal shortcomings that have hindered clinical development of metzincin inhibitors are low selectivity for the target enzyme, poor water solubility, and long-term toxicity. Over the last 15 years, a novel approach to improve solubility and bioavailability of metzincin inhibitors has been the synthesis of carbohydrate-based compounds. This strategy consists of linking a hydrophilic sugar moiety to an aromatic lipophilic scaffold. This review aims to describe the development of sugar-based and azasugar-based derivatives as metzincin inhibitors and their activity in several pathological models.
基质金属蛋白酶（MMPs）和去整合素金属蛋白酶（ADAMs）是属于金属锌蛋白酶超家族的锌依赖性内肽酶。金属锌蛋白酶活性上调是许多严重病理状况（如癌症、炎症和感染）的一个主要特征。在过去几十年中，已开发出许多类小分子来抑制这些酶。阻碍金属锌蛋白酶抑制剂临床开发的主要缺点是对目标酶的选择性低、水溶性差和长期毒性。在过去15年中，一种提高金属锌蛋白酶抑制剂溶解度和生物利用度的新方法是合成基于碳水化合物的化合物。该策略包括将亲水性糖部分连接到芳香族亲脂性支架上。本综述旨在描述基于糖和氮杂糖的衍生物作为金属锌蛋白酶抑制剂的开发及其在几种病理模型中的活性。
