Synthesis and binding monitoring of a new nanomolar PAMAM-based matrix metalloproteinases inhibitor (MMPIs)

Linda Cerofolini; Veronica Baldoneschi; Elisa Dragoni; Andrea Storai; Marianna Mamusa; Debora Berti; Marco Fragai; Barbara Richichi; Cristina Nativi

doi:10.1016/j.bmc.2016.11.028

Synthesis and binding monitoring of a new nanomolar PAMAM-based matrix metalloproteinases inhibitor (MMPIs)

Bioorg Med Chem. 2017 Jan 15;25(2):523-527. doi: 10.1016/j.bmc.2016.11.028. Epub 2016 Nov 19.

Authors

Linda Cerofolini¹, Veronica Baldoneschi², Elisa Dragoni², Andrea Storai², Marianna Mamusa², Debora Berti², Marco Fragai³, Barbara Richichi⁴, Cristina Nativi¹

Affiliations

¹ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, Via Sacconi 6, 50019 Sesto Fiorentino (FI), Italy.
² Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
³ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, Via Sacconi 6, 50019 Sesto Fiorentino (FI), Italy. Electronic address: fragai@cerm.unifi.it.
⁴ Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy. Electronic address: barbara.richichi@unifi.it.

PMID: 27914947
DOI: 10.1016/j.bmc.2016.11.028

Abstract

Dendrimers are efficient drug delivery systems particularly useful in ocular diseases. In particular, low generation PAMAM dendrimers are non-toxic and non-immunogenic and they provide an enhancement of the residence time of drugs in the eyes. In this context, the synthesis of the PAMAM-based matrix metalloproteinases inhibitor 5, is reported. In particular, we demonstrated that 5 strongly binds (18.0nM±2.5nM) MMP-9, the most relevant MMP responsible of ocular surface damages in induced dry eyes syndrome (DES).

Keywords: Dendrimers; Inhibitors; Metalloproteins; NMR spectroscopy; Sulphonamidic scaffold.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites / drug effects
Dendrimers / chemical synthesis
Dendrimers / chemistry
Dendrimers / pharmacology*
Dose-Response Relationship, Drug
Fluorometry
Humans
Matrix Metalloproteinase 9 / isolation & purification
Matrix Metalloproteinase 9 / metabolism*
Matrix Metalloproteinase Inhibitors / chemical synthesis*
Matrix Metalloproteinase Inhibitors / chemistry
Matrix Metalloproteinase Inhibitors / pharmacology*
Molecular Structure
Structure-Activity Relationship

Substances

Dendrimers
Matrix Metalloproteinase Inhibitors
PAMAM Starburst
Matrix Metalloproteinase 9