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

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.

SUBMITTER: Ammazzalorso A

PROVIDER: S-EPMC5085792 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Ammazzalorso Alessandra A De Filippis Barbara B Campestre Cristina C Laghezza Antonio A Marrone Alessandro A Amoroso Rosa R Tortorella Paolo P Agamennone Mariangela M

International journal of molecular sciences 20161022 10

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 identifi ...[more]

PMID: 27782083

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