title: Synthesis and biological evaluation of novel naphthalene compounds as potential antidepressant agents.
abstract: In this study, a series of novel naphthalene compounds were synthesized and screened for their antidepressant-like activities in vitro and in vivo. Their values for two descriptors (ClogP, tPSA) of the blood-brain barrier (BBB) were calculated for early assessment of the central nervous system (CNS) drug-likeness. Seven of them (6d, 6i, 6k, 6o, 6p, 6s and 6t) demonstrated potential protective effects on corticosterone-induced lesion of PC12 cells although they cannot repair the irreversible oxidant injury to PC12 cells by hydrogen peroxide. Compounds with promising neurorestorative activities (6k, 6o and 6p) were further evaluated for their in vivo effects by forced swim test (FST) and open field test (OFT) in C57 mice models. The FST results showed that compounds 6k, 6o and 6p remarkably reduced the immobility time of the tested mice. Among them, compound 6k was the most potent one, much more effective than Agomelatine and comparable to Fluoxetine. The OFT results showed that mice treated with compound 6k traveled a longer distance than those treated with Agomelatine or Fluoxetine, indicating a better general locomotor activity. The paper also proposed a possible binding mode of compound 6k with glucocorticoid receptor by docking study. The in vitro cytotoxicity data on HEK293 and L02 cells suggested compound 6k to be a promising antidepressant candidate for subsequent investigation.
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China; Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Pi
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: zhlxlll@163.com.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: dengyongy@sohu.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Shengyong
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: luo_youfu@scu.edu.cn.
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biotherapy and Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D009281:Naphthalenes
keywords: Corticosterone-induced; Depression; Forced swim test; Glucocorticoid receptor; Open field test; PC12 cells