Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors
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- 作者：Dr. Elisa Nuti ; Doretta Cuffaro ; Dr. Felicia D' ; Andrea ; Dr. Lea Rosalia ; Livia Tepshi ; Dr. Marina Fabbi ; Grazia Carbotti ; Dr. Silvano Ferrini ; Dr. Salvatore Santamaria ; Dr. Caterina Camodeca ; Dr. Lidia Ciccone ; Prof. Elisabetta Orlandini ; Susanna Nencetti ; Dr. Enrico A. Stura ; Dr. Vincent Dive and Prof. Armando Rossello
- 刊名：ChemMedChem
- 出版年：2016
- 出版时间：August 5, 2016
- 年：2016
- 卷：11
- 期：15
- 页码：1626-1637
- 全文大小：1594K
- ISSN：1860-7187
文摘
Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a β-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-β-d-glucopyranosyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified.