Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

In the five membered nitrogen containing heterocyclic family, 2-pyrazoline could be encountered as the most promising scaffold for antidepressant activity. Recently, this nucleus was endowed with remarkable attention in the inhibition of monoamine oxidase A (MAO-A), which is considered as the effective target for the management of depressive disorders. The literature survey revealed that the substitutions of 2-pyrazoline nucleus preferably at the N1, C3, and C5 positions showed remarkable effect in the central nervous system. Prasad et al. reported that the compounds possessing electron-releasing groups on both aromatic rings in positions 3 and 5 of substituted 2-pyrazolines considerably enhanced the antidepressant activity. Chimenti et al. demonstrated that either the N1 acetyl group or N1-propanoyl substitution in position 1 increased the potency and selectivity towards the MAO-A inhibition. Considering that 2-pyrazolines are promising class of antidepressants and in the light of aforementioned findings, we aimed to obtain some N1 substituted acetyl 2-pyrazoline derivatives with 3,5-unsubstituted/substituted phenyl 2-pyrazoline as the common scaffold, with anticipated MAO inhibitory and antidepressant activities. All the compounds inhibited hMAO-A selectively and potently. Their inhibition was found as competitive and reversible. The compounds showed quite high MAO-A inhibition were selected for evaluating of acute and chronic antidepressant activities by Porsolt Forced Swim Test in mice. The results displayed that antidepressant activity of these compounds show similar rates with that of moclobemide in chronic application.

Biography

Nesrin Gökhan-Kelekçi has completed her PhD in Pharmaceutical Chemistry at Hacettepe University and Postdoctoral studies from Braunschweig University of Technology and Kings College London. She is the Vice Dean of Faculty of Pharmacy of Hacettepe University. She has published more than 40 papers in reputed journals and has been serving as an Editorial Board Member of some journals.

Email: onesrin@hacettepe.edu.tr, onesrin@gmail.com