Design and Synthesis of Ionic Liquid-Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI-Coated Gold Nanoparticles

Felicia D'Andrea, Elisa Nuti, Stefano Becherini, Doretta Cuffaro, Elena Husanu, Caterina Camodeca, Elena De Vita, Maria Raffaella Zocchi, Alessandro Poggi, Cristina D'Arrigo, Valentina Cappello, Mauro Gemmi, Susanna Nencetti, Cinzia Chiappe, Armando Rossello

Research output: Contribution to journalArticlepeer-review

Abstract

Selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors endowed with improved hydrophilicity are highly sought for potential use in the treatment of lung and cardiovascular diseases. In the present paper, we modified the structure of a nanomolar MMP-12 inhibitor by incorporating an ionic liquid (IL) moiety to improve aqueous solubility. Four biologically active salts were obtained by linking the sulfonamide moiety of the MMP-12 inhibitor to imidazolium-, pyrrolidinium-, piperidinium-, and DABCO-based ILs. The imidazolium-based bioactive salt was tested on human recombinant MMPs and on monocyte-derived dendritic cells, showing activity similar to that of the parent compound, but improved water solubility. The imidazolium-based bioactive salt was then used to prepare electrostatically stabilized MMP inhibitor-coated gold nanoparticles (AuNPs) able to selectively bind MMP-12. These AuNPs were used to study subcellular localization of MMP-12 in monocyte-derived dendritic cells by transmission electron microscopy analysis.

Original languageEnglish
Pages (from-to)686-698
Number of pages13
JournalChemMedChem
Volume14
Issue number6
DOIs
Publication statusPublished - Mar 22 2019

Keywords

  • gold nanoparticles
  • ionic liquids
  • metalloproteinases
  • MMP-12

ASJC Scopus subject areas

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

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