Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies
Articolo
Data di Pubblicazione:
2016
Abstract:
Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
MMPs; docking; inhibitors; isoquinoline; molecular dynamics; non-zinc-binding group; quinoline; ureas
Elenco autori:
Ammazzalorso, Alessandra; DE FILIPPIS, Barbara; Campestre, Cristina; Laghezza, Antonio; Marrone, Alessandro; Amoroso, Rosa; Tortorella, Paolo; Agamennone, Mariangela
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