Synthesis, In-silico analysis and Antidepressant activity of New Pyrazoline Analogs

Abstract

Objective: This study is undertaken to design and synthesize new pyrazoline derivatives and evaluate their anti-depressant efficacy by In-silico and In-vivo studies. 
Methodology: Pyrazoline derivatives (PY1-PY9) were yielded by the cyclization of chalcones(C1-C9) with phenylhydrazine.HCl in glacial acetic acid. FT-IR, 1H-NMR, and Mass spectral data established the structures of the newly synthesized compounds. In-silico analysis was carried out using Schrodinger 2018-3 suite device Maestro and docked to the binding site of the Human MAO-A enzyme(2Z5X). In-vivo anti-depressant study was performed by Tail suspension method and Forced swimming test. 
Results: The confirmation of the probable mechanism by which the compounds exhibit neuropharmacological interactions resulted from the interaction of the compounds with the residues of the binding sites, namely, ASP 46. This shows that the compounds have a profound affinity towards MAO-A target protein. In addition, the non-toxic nature of the compounds was established by the LAZAR program. Compounds PY3 and PY2 depicted the best docking scores (-9.894 and -9.766 respectively), and subsequent In-vivo analysis established that substantial anti-depressant efficacy upon comparison to the standard was demonstrated by compounds PY2 and PY8 in FST and compounds PY2 and PY3 in the TST. 
Conclusion: The data indicated that among the synthesized pyrazoline derivatives, 4-(1-ethyl-5-(phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol (PY8) , 4-(1-ethyl-5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol(PY2) and 4-(1-ethyl-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol (PY3) showed good anti-depressive activity with potent inhibitory activity against MAO-A target protein.

:TJPS-2020-0130.R2