Facile One-Pot Synthesis Methodology for Nitrogen-Containing Heterocyclic Derivatives of 3,5-Disubstituted 4,5-Dihydro-1H-Pyrazole, Their Biological Evaluation and Molecular Docking Studies

Abstract

A series of 2-pyrazoline derivatives (PS-1 to PS-16) were synthesized by reacting different aromatic/heteroaromatic aldehydes and ketones, in a two-step reaction through Claisen – Schmidt condensation, followed by cyclization of the resulting chalcones with hydrazine hydrate in the presence of a base using conventional and microwave approaches. The synthesized derivatives were characterized by various physicochemical methods including IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopic data and elemental analysis. The antidepressant and anti-anxiety activities were evaluated using suitable animal models. Compounds PS-3, and PS-14 showed noticeable antidepressant activity, by reducing the duration of immobility in both tests, while compounds PS-9 and PS-12 were found to possess good anxiolytic activity (by increasing the number of arm entries and open arm exploratory time) at the tested doses (50 and 100 mg/kg b.w.) in comparison to standard drugs imipramine and diazepam, respectively. In order to elucidate binding interactions of the synthesized derivatives to the MAO-A target protein, molecular docking was employed which demonstrated the key interactions with amino acid residues Phe208, Asn181, and Tyr407 at the binding site. Further, the ADME properties of the synthesized derivatives were predicted and found to fall within the stated limits.