Developments in Carbohydrate-Based Metzincin Inhibitors

被引:4
|
作者
Cuffaro, Doretta [1 ]
Nuti, Elisa [1 ]
D'Andrea, Felicia [1 ]
Rossello, Armando [1 ]
机构
[1] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy
关键词
carbohydrates; glycoconjugates; MMPs; ADAMs; iminosugars; metzincin inhibitors; MATRIX-METALLOPROTEINASE INHIBITORS; STRUCTURE-BASED DESIGN; CATALYTIC DOMAIN; IN-VITRO; CRYSTAL-STRUCTURE; HIGHLY POTENT; CARTILAGE DEGRADATION; SELECTIVE INHIBITORS; HEMOPEXIN DOMAIN; 17; ADAM17;
D O I
10.3390/ph13110376
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:1 / 21
页数:21
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