title: Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT2A Receptor Antagonists.
abstract: 5-Hydroxytryptamine type 2A (5-HT2A) receptor is an important target for developing innovative antipsychotic agents in neuropsychiatric disorder therapies. To search for 5-HT2A receptor antagonists, a new indole alkaloid termed 6-bromo-N-propionyltryptamine (1), together with one known homologue 6-bromo-N-acetyltryptamine (2) were isolated and identified from a marine bacterium Pseudoalteromonas rubra QD1-2. Compound 1 with an N-propionyl side chain exhibited stronger 5-HT2A receptor antagonist activity than that of N-acetyl derivative (2), indicating that 6-bromotryptamine analogues with a longer chain acyl group perhaps displayed a more potent capacity to the target. Therefore, a series of new 6-bromotryptamine analogues (3-7) with different chain length of the acyl group (C4-C8) were prepared and evaluated activity against 5-HT2A receptor. Remarkably, 6-bromo-N-hexanoyltryptamine (5) displayed the most effective inhibitory activity, which was 5-fold stronger than that of the parent compound 1 and showed 70% efficacy of the positive control (ketanserin tartrate).
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. huahua20062008@126.com.|College of Pharmacy, Jinan University, Guangzhou 510632, China. huahua20062008@126.com.
authors.forename: Lijian
authors.initials: L
authors.lastname: Ding
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. heshan@nbu.edu.cn.|Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo 315211, China. heshan@nbu.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo 315211, China. wuweixiehou@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. jinhaixiao@nbu.edu.cn.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Jin
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo 315211, China. zhupeng@nbu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. zhangjinrong@nbu.edu.cn.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. happyjelly@yeah.net.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Laboratory of Marine Natural Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China. 23yuanye@163.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo 315211, China. yanxiaojun@nbu.edu.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yan
mesh_terms: D014150:Antipsychotic Agents / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D031161:Pseudoalteromonas / Q000737:chemistry*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000737:chemistry / Q000302:isolation & purification*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D014150:Antipsychotic Agents; D058830:Serotonin 5-HT2 Receptor Antagonists; D014363:Tryptamines
keywords: 5-HT2A receptor; 6-bromotryptamine; Pseudoalteromonas rubra; antagonist