Design and synthesis of new series of coumarin-aminopyran derivatives possessing potential anti-depressant-like activity.

A new series of coumarin based aminopyran derivatives were designed, synthesized and evaluated for their preclinical antidepressant effect on Swiss albino mice. Among the series, compounds 21, 25, 26, 27, 32 and 33 exhibited significant activity profile in forced swimming test (FST). Compound 27 was most efficacious, which at a very low dose of 0.5mg/kg reduced the time of immobility by 86.5% as compared to the standard drug fluoxetine (FXT) which reduced the immobility time by 69.8% at the dose of 20mg/kg, ip. In addition, all active compounds were screened in dose dependent manner (at doses of 0.25, 0.5, 1mg/kg ip) in FST and tail suspension test (TST). Interestingly, all active compounds did not caused any significant alteration of locomotor activity in mice as compared to control, indicating that the hybrids did not produce any motor impairment effects. The results indicate that coumarin-aminopyran derivatives may have potential therapeutic value for the management of mental depression.

Synthesis and evaluation of new 3-phenylcoumarin derivatives as potential antidepressant agents.

A series of amine substituted 3-phenyl coumarin derivatives were designed and synthesized as potential antidepressant agents. In preliminary screening, all compounds were evaluated in forced swimming test (FST), a model to screen antidepressant activity in rodents. Among the series, compounds 5c and 6a potentially decreased the immobility time by 73.4% and 79.7% at a low dose of 0.5 mg/kg as compared to standard drug fluoxetine (FXT) which reduced the immobility time by 74% at a dose of 20 mg/kg, ip. Additionally, these active compounds also exhibited significant efficacy in tail suspension test (TST) (another model to screen antidepressant compounds). Interestingly, rotarod and locomotor activity tests confirmed that these two compounds do not have any motor impairment effect and neurotoxicity in mice. Our studies demonstrate that the new 3-phenylcoumarin derivatives may serve as a promising antidepressant lead and hence pave the way for further investigation around this chemical space.