JOURNAL OF PHARMACOLOGY AND
BIOMEDICINE
ISSN.2456-8244
In the present study, a series of novel pyridine-linked pyrazoline derivatives (5a-e) were synthesized using chalcone intermediates and evaluated for their antidepressant potential. The synthesized compounds were prepared through Claisen-Schmidt condensation followed by cyclization with substituted phenylhydrazines. The synthesized compounds were obtained in satisfactory yields ranging from 70-73%. Acute toxicity studies revealed no signs of toxicity or mortality at an oral dose of 2000 mg/kg, indicating a favorable safety profile. Antidepressant activity was assessed using the Tail Suspension Test (TST) in mice, with fluoxetine serving as the reference standard. Among the synthesized derivatives, compound 5c bearing a para-hydroxyl substituent exhibited the most pronounced antidepressant-like activity, producing the lowest immobility time (15.20 ± 0.663 s) among the test compounds and approaching the activity of fluoxetine. Compounds 5b and 5e demonstrated moderate activity, whereas compound 5d showed minimal antidepressant effect. Structure-activity relationship analysis indicated that para-substituted electron- donating groups enhanced antidepressant activity more effectively than electron-withdrawing substituents. These findings identify compound 5c as a promising lead molecule for further development of novel antidepressant agents.
NAMES:
ONLINE ISSN:24568244
Keywords: Pyrazoline, anti-depressant, tail suspension test, in-silico ADMET, structure activity relationship
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