Modeling of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives by several conformational searching tools and molecular docking

Mohammad Goodarzi, Alina Bora, Ana Borota, Simona Funar-Timofei, Sorin Avram, Yvan Vander Heyden

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Neutrophil elastase, a serine proteinase from the chymotrypsin family, has been the object of comprehensive experimental and theoretical studies to develop efficient human neutrophil elastase inhibitors. The serine protease has been linked to the pathology of a variety of inflammatory diseases, making it an attractive target for the development of anti-inflammatory compounds. In this work, we have built a common binding model of the 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives into the human neutrophil elastase binding site. This was accomplished through a comparative conformational analysis (using OMEGA, HYPERCHEM, and MOPAC software) of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one inhibitors followed by rigid and flexible molecular docking (by the FRED and GLIDE programs) into the target protein. We conclude that OMEGA software generates the most representative conformers to model the protein-ligand interactions.

Original languageEnglish (US)
Pages (from-to)2194-2203
Number of pages10
JournalCurrent Pharmaceutical Design
Volume19
Issue number12
DOIs
StatePublished - May 21 2013

Keywords

  • Benzoxazinone derivative
  • Biologically active conformation
  • Conformational analysis
  • Human neutrophil elastase inhibitor
  • Molecular docking

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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