Objective: This study is undertaken to design and synthesize new pyrazoline derivatives and to evaluate their antidepressant efficacy by in silico and in vivo studies. Materials and Methods: The title compounds 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 Human MAO-A enzyme (2Z5X). In vivo antidepressant study was performed by tail suspension method and forced swimming test. Results: Confirmation of the probable mechanism by which the compounds exhibit neuropharmacological interactions, resulted from the interaction of the compounds to the residues of the binding sites, namely, ASP 46. This shows that the compounds have a profound affinity toward MAO-A target protein. In addition, the non-toxic nature of the compounds was established by 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 antidepressant efficacy on 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 the synthesized pyrazoline derivatives, namely, 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.
Faculty of Pharmaceutical Sciences, Chulalongkorn University
Aggarwal, Natasha Naval; Gatphoh, Banylla Felicity Dkhar; Kumar, M. Vijay; Ghetia, Sawan; and Revanasiddappa, B. C.
"Synthesis, in silico analysis and
antidepressant activity of pyrazoline analogs,"
The Thai Journal of Pharmaceutical Sciences: Vol. 45:
1, Article 4.
Available at: https://digital.car.chula.ac.th/tjps/vol45/iss1/4