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Molecular Diversity

, Volume 22, Issue 2, pp 383–395 | Cite as

An integrated structure- and pharmacophore-based MMP-12 virtual screening

Original Article
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Abstract

MMP-12 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades elastin. The main pathologic role of MMP-12 overexpression was suggested to be associated with pathogenesis mechanism of inflammatory respiratory diseases and atherosclerosis. An integrated ligand- and structure-based virtual screening was employed in hope of finding inhibitors with new scaffolds and selectivity for MMP-12. Seven compounds among 18 experimentally tested compounds had a measurable effect on the inhibition of MMP-12 enzyme. Our results demonstrated the applicability of the developed pharmacophore model and selected crystal structure (PDB code: 3F17) to discover new MMP-12 inhibitors. The receptor structure was selected based on cross-docking results. Here, we report the discovery of new class of MMP-12 inhibitors that could be used for lead optimization. For the inhibition of MMP-12, the significance of its interactions with the catalytic residues Glu219 and Ala182 was emphasized through the inspection of the docking poses.

Keywords

Docking Matrix metalloproteinases MMP-12 Pharmacophore Virtual screening 

Notes

Acknowledgements

This work was supported in part by Mashhad University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors confirm that this article’s content contains no conflict of interest.

Supplementary material

11030_2017_9804_MOESM1_ESM.docx (399 kb)
Supplementary material 1 (docx 399 KB)

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nanotechnology Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Biotechnology, School of PharmacyMashhad University of Medical SciencesMashhadIran
  3. 3.Pharmaceutical Research Center, Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran

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