In Silico Screening of Novel α1-GABA_A Receptor PAMs towards Schizophrenia Based on Combined Modeling Studies of Imidazo [1,2-a]-Pyridines.

ABSTRACT: The ionotropic GABA_A receptor (GABA_AR) has been proven to be an important target of atypical antipsychotics. A novel series of imidazo [1,2-a]-pyridine derivatives, as selective positive allosteric modulators (PAMs) of α1-containing GABA_ARs with potent antipsychotic activities, have been reported recently. To better clarify the pharmacological essentiality of these PAMs and explore novel antipsychotics hits, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, pharmacophore modeling, and molecular dynamics (MD) were performed on 33 imidazo [1,2-a]-pyridines. The constructed 3D-QSAR models exhibited good predictive abilities. The dockings results and MD simulations demonstrated that hydrogen bonds, π-π stackings, and

SUBMITTER: Zheng X 

PROVIDER: S-EPMC8431797 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature