Novel GABA-AT inhibitors: QSAR and docking based virtual screening of phenyl substituted β-phenyl ethylidene hydrazine analogues

摘要

In the present study, Lamarckian genetic algorithm (LGA) based docking (AutoDock 4.0), k-nearest neighbor molecular field analysis (kNN-MFA) based 3D-QSAR, fragment and knowledge based approach were used to generate and screen a virtual library. Three analogues of β-phenylethylidene hydrazine (PEH) were designed as novel GABA-AT inhibitors. The docking interactions of N-[(1E) 2-phenylethylidene]pyridin-2-amine (S ₄ ), (2E)-1-phenyl-2-(2-phenylethylidene)hydrazine (S ₈ ) and (1E)-1-ethylidene-2-phenylhydrazine (S ₂₁ ) with Lys 329 appears to be in close proximity and explains the high GABA-AT selectivity observed.