Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties

Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydrois...

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Detalles Bibliográficos
Autores principales: Dai, Hongbin, Jiao, Qiong, Liu, Tian, You, Qidong, Jiang, Zhengyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151508/
https://www.ncbi.nlm.nih.gov/pubmed/28902165
http://dx.doi.org/10.3390/molecules22091541
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author Dai, Hongbin
Jiao, Qiong
Liu, Tian
You, Qidong
Jiang, Zhengyu
author_facet Dai, Hongbin
Jiao, Qiong
Liu, Tian
You, Qidong
Jiang, Zhengyu
author_sort Dai, Hongbin
collection PubMed
description Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation.
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spelling pubmed-61515082018-11-13 Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties Dai, Hongbin Jiao, Qiong Liu, Tian You, Qidong Jiang, Zhengyu Molecules Article Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation. MDPI 2017-09-13 /pmc/articles/PMC6151508/ /pubmed/28902165 http://dx.doi.org/10.3390/molecules22091541 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dai, Hongbin
Jiao, Qiong
Liu, Tian
You, Qidong
Jiang, Zhengyu
Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title_full Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title_fullStr Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title_full_unstemmed Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title_short Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties
title_sort development of novel nrf2/are inducers bearing pyrazino[2,1-a]isoquinolin scaffold with potent in vitro efficacy and enhanced physicochemical properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151508/
https://www.ncbi.nlm.nih.gov/pubmed/28902165
http://dx.doi.org/10.3390/molecules22091541
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