Issue 28, 2021, Issue in Progress
From the journal:

RSC Advances

Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics†

Lanchang Gao,‡ab   Chao Hao,‡b   Ru Ma,a   Jiali Chen,b   Guisen Zhangab  and  Yin Chen ORCID logo *a  

* Corresponding authors

a Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, China
E-mail: 2019000015@jou.edu.cn
Fax: +86-518-85586628
Tel: +86-518-85586628

b Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

Abstract

In this study, we designed and synthesized a novel series of multi-receptor ligands as polypharmacological antipsychotic agents by using a multi-receptor affinity strategy. Among them, 3w combines a multi-receptor mechanism with high mixed affinities for D2, 5-HT1A, 5-HT2A and H3 receptors, and low efficacy at the off-target receptors (5-HT2C, H1 and α1 receptor) and human ether-à-go-go-related gene (hERG) channel. In addition, compound 3w exhibits favorable antipsychotic drug-like activities in in vivo assessment. An animal behavioral study revealed that compound 3w significantly reverses apomorphine-induced climbing and MK-801-induced hyperactivity, and avoidance behavior in the CAR test, with a high threshold for catalepsy. Moreover, compound 3w demonstrates memory enhancement in a novel object recognition task and low liabilities for weight gain and hyperprolactinemia in a long-term metabolic adverse effects model. Thus, 3w was selected as an antipsychotic candidate for further development.

Graphical abstract: Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics

About
Cited by
Related
Download options Please wait...

Supplementary files

Article information

DOI
https://doi.org/10.1039/D1RA02426D
Article type
Paper
Submitted
26 Mar 2021
Accepted
26 Apr 2021
First published
07 May 2021
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2021,11, 16931-16941

Permissions

Request permissions

Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics

L. Gao, C. Hao, R. Ma, J. Chen, G. Zhang and Y. Chen, RSC Adv., 2021, 11, 16931 DOI: 10.1039/D1RA02426D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements