title: Modeling of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one derivatives by several conformational searching tools and molecular docking.
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.
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. mgoodarz@vub.ac.be
authors.forename: Mohammad
authors.initials: M
authors.lastname: Goodarzi
authors.forename: Alina
authors.initials: A
authors.lastname: Bora
authors.forename: Ana
authors.initials: A
authors.lastname: Borota
authors.forename: Simona
authors.initials: S
authors.lastname: Funar-Timofei
authors.forename: Sorin
authors.initials: S
authors.lastname: Avram
authors.forename: Yvan Vander
authors.initials: YV
authors.lastname: Heyden
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D048588:Benzoxazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D019295:Computational Biology; D062126:Databases, Chemical; D030562:Databases, Protein; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005466:Fluorocarbons; D006801:Humans; D006860:Hydrogen Bonding; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009025:Morpholines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: C583258:2-pyridin-3-yl-benzo(d)(1,3)oxazin-4-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D048588:Benzoxazines; D005466:Fluorocarbons; D008024:Ligands; D009025:Morpholines; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C088380:MDL 101146; D019272:Leukocyte Elastase