Discovery and synthesis of novel 3-phenylcoumarin derivatives as antidepressant agents

• Published in: Bioorganic & medicinal chemistry letters 2011-04, Vol.21 (7), p.1937-1941
• Main Authors: Sashidhara, Koneni V., Kumar, Abdhesh, Chatterjee, Manavi, Rao, K. Bhaskara, Singh, Seema, Verma, Anil Kumar, Palit, Gautam
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antidepressant activity; Antidepressants; Antidepressive Agents - chemical synthesis; Antidepressive Agents - chemistry; Antidepressive Agents - pharmacology; Biological and medical sciences; Coumarin; Coumarins - chemical synthesis; Coumarins - chemistry; Coumarins - pharmacology; Dose-Response Relationship, Drug; Drug Discovery; Fluoxetine; Forced swim test; imipramine; Male; Medical sciences; Mice; Neuropharmacology; Neurotoxicity; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; reference standards; scaffolds; Spectrophotometry, Infrared; Stress, Physiological; Swimming; Synthesis; tail; Tail suspension test
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.02.040

A series of novel 3-phenylcoumarin derivatives have been synthesized and evaluated for their in vivo antidepressant activities. The most active compound 6 was selected as lead compound for further antidepressant research. A series of 3-phenylcoumarins were synthesized and screened for potential antidepressant activity by tail suspension test (TST) in mice. Three compounds ( 6, 7 and 13) exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration (% DID). In addition, the active antidepressant compounds were subsequently studied at their most effective dose and activity of these compounds were confirmed in forced swimming test (FST) animal model, in which the compounds at a low dose of 0.5 mg/kg significantly decreased the immobility time and exhibited greater efficacy than the reference standards fluoxetine and imipramine. The potent compounds did not show any neurotoxicity in the rotarod test and the preliminary results are promising enough to warrant further studies around this scaffold.