154493-27-3Relevant academic research and scientific papers
Synthesis, in vitro activity, and three-dimensional quantitative Structure-activity relationship of novel hydrazine inhibitors of human vascular adhesion protein-1
Nurminen, Elisa M.,Pihlavisto, Marjo,Lázár, László,Szakonyi, Zsolt,Pentik?inen, Ulla,Fül?p, Ferenc,Pentik?inen, Olli T.
experimental part, p. 6301 - 6315 (2010/10/20)
Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those seen in the crystal structures to bind. Combining the data from molecular dynamics simulations, docking, and in vitro measurements, the three-dimensional quantitative Structure-activity relationship (3D QSAR) models for VAP-1 (q2LOO: 0.636; r2: 0.828) and MAOs (q2LOO: 0.749, r2: 0.840) were built and employed in the development of selective VAP-1 inhibitors.
