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.

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

D'Andrea, Felicia;Nuti, Elisa;Becherini, Stefano;Cuffaro, Doretta;Husanu, Elena;Camodeca, Caterina;Nencetti, Susanna;Chiappe, Cinzia;Rossello, Armando
2019-01-01

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.
2019
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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/987706
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