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Design and Synthesis of Ionic Liquid‐Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI‐Coated Gold Nanoparticles
Author(s) -
D'Andrea Felicia,
Nuti Elisa,
Becherini Stefano,
Cuffaro Doretta,
Husanu Elena,
Camodeca Caterina,
De Vita Elena,
Zocchi Maria Raffaella,
Poggi Alessandro,
D'Arrigo Cristina,
Cappello Valentina,
Gemmi Mauro,
Nencetti Susanna,
Chiappe Cinzia,
Rossello Armando
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800733
Subject(s) - moiety , ionic liquid , chemistry , colloidal gold , matrix metalloproteinase inhibitor , matrix metalloproteinase , solubility , combinatorial chemistry , nanoparticle , biophysics , sulfonamide , organic chemistry , materials science , biochemistry , nanotechnology , catalysis , biology
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.