title: Synthesis and structure-activity relationship of novel cinnamamide derivatives as antidepressant agents.
abstract: Cinnamamide 3a, a leading compound with antidepressant-like activity, and its derivatives were synthesized and their antidepressant activity and structure-activity relationship were investigated. Most of the compounds with trifluoromethyl group in methylenedioxyphenyl moiety (3f, 4b-c and 6a-b) exhibited significant antidepressant activity, measured in terms of percentage decrease in immobility duration by tail suspension test. In addition, the dose-dependent antidepressant effect of the most potent compound 3f was subsequently confirmed in tail suspension test and forced swim test. The test results showed that 3f was equal to or more effective than the standard drug fluoxetine at a concentration of 10mg/kg. Furthermore, compound 3f did not show any central nervous system stimulant properties in the open-field test and the preliminary results were promising enough to warrant further detailed antidepressant research around this scaffold.
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China; School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: maxiaohui@tasly.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ma
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Yuanpeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Wangyi
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Yahu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Shuiping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Guocheng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Tianjin Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin 300410, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D031701:Piper / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D001688:Biological Products; D002934:Cinnamates; C411088:cinnamamide
keywords: Antidepressant agents; Cinnamamide derivatives; Forced swim; Structure–activity relationship; Tail suspension