1. Sodium hyaluronate-g-2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide with enhanced affinity towards MMP12 catalytic domain to be used as visco-supplement with increased degradation resistance.
- Author
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Leone G, Pepi S, Consumi M, Lamponi S, Fragai M, Martinucci M, Baldoneschi V, Francesconi O, Nativi C, and Magnani A
- Subjects
- Catalytic Domain, Chondrocytes drug effects, Hyaluronic Acid chemical synthesis, Hyaluronic Acid metabolism, Hyaluronic Acid toxicity, Hydroxamic Acids chemical synthesis, Hydroxamic Acids metabolism, Hydroxamic Acids toxicity, Matrix Metalloproteinase 12 chemistry, Matrix Metalloproteinase 12 metabolism, Matrix Metalloproteinase Inhibitors chemical synthesis, Matrix Metalloproteinase Inhibitors metabolism, Matrix Metalloproteinase Inhibitors toxicity, Protein Binding, Sulfonamides chemical synthesis, Sulfonamides metabolism, Sulfonamides toxicity, Viscoelastic Substances chemical synthesis, Viscoelastic Substances metabolism, Viscoelastic Substances toxicity, Hyaluronic Acid pharmacology, Hydroxamic Acids pharmacology, Matrix Metalloproteinase Inhibitors pharmacology, Sulfonamides pharmacology, Viscoelastic Substances pharmacology
- Abstract
The present paper describes the functionalization of sodium hyaluronate (NaHA) with a small molecule (2-((N-(6-aminohexyl)-4-methoxyphenyl)sulfonamido)-N-hydroxyacetamide) (MMPI) having proven inhibitory activity against membrane metalloproteins involved in inflammatory processes (i.e. MMP12). The obtained derivative (HA-MMPI) demonstrated an increased resistance to the in-vitro degradation by hyaluronidase, viscoelastic properties close to those of healthy human synovial fluid, cytocompatibility towards human chondrocytes and nanomolar affinity towards MMP 12. Thus, HA-MMPI can be considered a good candidate as viscosupplement in the treatment of knee osteoarticular disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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