Synthesis of Chromen-1-phenylpropan-1-one Derivatives and their Antidepressant/ Anticonvulsant Activities

Abstract

Background: Coumarin and chalcone are important secondary plant metabolites that exhibit a range of biological activities. Accordingly, the synthetic derivatives and analogs of these molecules have attracted attention as potential pharmacological agents Objective: This study aims to study new antidepressants with high biological activity and low side effects, and to provide a basis for the treatment of epilepsy and depression. Method: In this study, a series of chalcone derivatives containing a coumarin moiety (2a–2s) were designed, synthesized, and evaluated using classic antidepressant and anticonvulsant mouse models. Results: Forced swimming test results revealed that all but one of the compounds tested significantly decreased immobility time at a dose of 10 mg/kg and exhibited some antidepressant activities. Furthermore, compounds 2a, 2c, 2h, and 2k exhibited relatively high antidepressant effects in a dosedependent manner from 10 to 30 mg/kg. Maximal electroshock seizure tests showed that compounds 2a, 2b, 2c, 2h, 2l, 2r, and 2s exhibited anticonvulsant activities at a dose of 30 mg/kg. Conclusion: Accordingly, compounds 2a, 2c, and 2h showed promise as antidepressant adjunct therapy agents for treating depression in patients with epilepsy. Chromatographic neurochemical analysis of the mouse brain tissue revealed that the antidepressant effects of the compounds may be mediated by an increase in serotonin level.