Background: A series of newly synthesized compounds structurally related to
Aripiprazole and Brexpiprazole, atypical antipsychotic and antidepressant used clinically for the
treatment of schizophrenia, depression and bipolar disorder have been prepared and characterized by
Elemental analysis, FT-IR, 1H NMR, 13C NMR, HSQC (2D NMR) and Mass spectrometry. All
the compounds have been docked against, human A2A Adenosine receptor, human β2-Adrenergic
G-Protein Coupled Receptor (GPCR) and ADME properties ware also evaluated.
Objective: We focused on screening the neuroleptic activity of the synthesized drug molecules with
different anti-psychotic animal models.
Methods: All the drug molecules (10mg/kg) and also standard drug Aripiprazole (5mg/kg) were
administered to their individual groups with 8 different animal models. Docking studies were carried
out by Schrodinger 9.5 software to predict the antipsychotic activity and the pharmacokinetic
properties were subjected to QIKPROP3.7 (Qikprop)
module of Schrödinger software to determine
Results: Both the receptor and ligand interaction shows an excellent dock score. ADME properties
were also evaluated in the desirable range; finally these compounds have orally drug-likeness
property. The results basically pointed out the fact that mutually the test molecules and control group
may have the property to improve the positive symptoms of schizophrenia by reducing the dopamine
levels of dopaminergic neurons of the brain.
Conclusion: Docked against the protein to determine the Binding Energy, Glides core, Hydrogen
bond, Total Intermolecular Energy and Interacting residues. ADME properties have been determined
and obey the Lipinski's rule of five for drug likeness property. The synthesized compounds are used
against Aripiprazole as a standard drug. The result has shown a promising effect in reducing the
positive symptoms of psychosis in rats by sinking the dopamine levels in the frontal cortical region of