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Int. J. Mol. Sci. 2016, 17(10), 1768; doi:10.3390/ijms17101768

Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

1
Dipartimento di Farmacia, Università “G. d’Annunzio” Chieti, Via dei Vestini 31, 66100 Chieti, Italy
2
Dipartimento di Farmacia-Scienze del Farmaco, Università “A. Moro” Bari, Via Orabona 4, 70125 Bari, Italy
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Academic Editors: Claudiu T. Supuran and Koji Sode
Received: 29 July 2016 / Revised: 10 October 2016 / Accepted: 14 October 2016 / Published: 22 October 2016
(This article belongs to the Special Issue Enzyme-Inhibitor Interaction as Examples of Molecular Recognition)
View Full-Text   |   Download PDF [9993 KB, uploaded 24 October 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. View Full-Text
Keywords: MMPs; inhibitors; molecular dynamics; docking; quinoline; isoquinoline; ureas; non-zinc-binding group MMPs; inhibitors; molecular dynamics; docking; quinoline; isoquinoline; ureas; non-zinc-binding group
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MDPI and ACS Style

Ammazzalorso, A.; De Filippis, B.; Campestre, C.; Laghezza, A.; Marrone, A.; Amoroso, R.; Tortorella, P.; Agamennone, M. Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies. Int. J. Mol. Sci. 2016, 17, 1768.

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