Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors

Elisa Nuti, Doretta Cuffaro, Felicia D'Andrea, Lea Rosalia, Livia Tepshi, Marina Fabbi, Grazia Carbotti, Silvano Ferrini, Salvatore Santamaria, Caterina Camodeca, Lidia Ciccone, Elisabetta Orlandini, Susanna Nencetti, Enrico A. Stura, Vincent Dive, Armando Rossello

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1626-1637
Number of pages12
JournalChemMedChem
DOIs
Publication statusPublished - Aug 5 2016

Fingerprint

Matrix Metalloproteinase 12
Matrix Metalloproteinase Inhibitors
Sugars
Water
Glycoconjugates
Glucosamine
Hydrophilicity
Matrix Metalloproteinases
Hydrophobic and Hydrophilic Interactions
Solubility
Lung Diseases
Assays
Cardiovascular Diseases
Therapeutics

Keywords

  • carbohydrates
  • drug discovery
  • glycoconjugates
  • metalloproteins
  • MMP-12 inhibitors

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

Cite this

Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. / Nuti, Elisa; Cuffaro, Doretta; D'Andrea, Felicia; Rosalia, Lea; Tepshi, Livia; Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano; Santamaria, Salvatore; Camodeca, Caterina; Ciccone, Lidia; Orlandini, Elisabetta; Nencetti, Susanna; Stura, Enrico A.; Dive, Vincent; Rossello, Armando.

In: ChemMedChem, 05.08.2016, p. 1626-1637.

Research output: Contribution to journalArticle

Nuti, E, Cuffaro, D, D'Andrea, F, Rosalia, L, Tepshi, L, Fabbi, M, Carbotti, G, Ferrini, S, Santamaria, S, Camodeca, C, Ciccone, L, Orlandini, E, Nencetti, S, Stura, EA, Dive, V & Rossello, A 2016, 'Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors', ChemMedChem, pp. 1626-1637. https://doi.org/10.1002/cmdc.201600235
Nuti, Elisa ; Cuffaro, Doretta ; D'Andrea, Felicia ; Rosalia, Lea ; Tepshi, Livia ; Fabbi, Marina ; Carbotti, Grazia ; Ferrini, Silvano ; Santamaria, Salvatore ; Camodeca, Caterina ; Ciccone, Lidia ; Orlandini, Elisabetta ; Nencetti, Susanna ; Stura, Enrico A. ; Dive, Vincent ; Rossello, Armando. / Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. In: ChemMedChem. 2016 ; pp. 1626-1637.
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