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Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones
H(3)R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1H)-ones was prepared to screen their H(3)R antagonistic activities and antiseizure effects. The majority of the targe...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144301/ https://www.ncbi.nlm.nih.gov/pubmed/37110645 http://dx.doi.org/10.3390/molecules28083408 |
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author | Hua, Yi Song, Mingxia Guo, Qiaoyue Luo, Yiqin Deng, Xianqing Huang, Yushan |
author_facet | Hua, Yi Song, Mingxia Guo, Qiaoyue Luo, Yiqin Deng, Xianqing Huang, Yushan |
author_sort | Hua, Yi |
collection | PubMed |
description | H(3)R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1H)-ones was prepared to screen their H(3)R antagonistic activities and antiseizure effects. The majority of the target compounds displayed a potent H(3)R antagonistic activity. Among them, compounds 2a, 2c, 2h, and 4a showed submicromolar H(3)R antagonistic activity with an IC(50) of 0.52, 0.47, 0.12, and 0.37 μM, respectively. The maximal electroshock seizure (MES) model screened out three compounds (2h, 4a, and 4b) with antiseizure activity. Meanwhile, the pentylenetetrazole (PTZ)-induced seizure test gave a result that no compound can resist the seizures induced by PTZ. Additionally, the anti-MES action of compound 4a fully vanished when it was administrated combined with an H(3)R agonist (RAMH). These results showed that the antiseizure role of compound 4a might be achieved by antagonizing the H(3)R receptor. The molecular docking of 2h, 4a, and PIT with the H(3)R protein predicted their possible binding patterns and gave a presentation that 2h, 4a, and PIT had a similar binding model with H(3)R. |
format | Online Article Text |
id | pubmed-10144301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101443012023-04-29 Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones Hua, Yi Song, Mingxia Guo, Qiaoyue Luo, Yiqin Deng, Xianqing Huang, Yushan Molecules Article H(3)R is becoming an attractive and promising target for epilepsy treatment as well as the discovery of antiepileptics. In this work, a series of 6-aminoalkoxy-3,4-dihydroquinolin-2(1H)-ones was prepared to screen their H(3)R antagonistic activities and antiseizure effects. The majority of the target compounds displayed a potent H(3)R antagonistic activity. Among them, compounds 2a, 2c, 2h, and 4a showed submicromolar H(3)R antagonistic activity with an IC(50) of 0.52, 0.47, 0.12, and 0.37 μM, respectively. The maximal electroshock seizure (MES) model screened out three compounds (2h, 4a, and 4b) with antiseizure activity. Meanwhile, the pentylenetetrazole (PTZ)-induced seizure test gave a result that no compound can resist the seizures induced by PTZ. Additionally, the anti-MES action of compound 4a fully vanished when it was administrated combined with an H(3)R agonist (RAMH). These results showed that the antiseizure role of compound 4a might be achieved by antagonizing the H(3)R receptor. The molecular docking of 2h, 4a, and PIT with the H(3)R protein predicted their possible binding patterns and gave a presentation that 2h, 4a, and PIT had a similar binding model with H(3)R. MDPI 2023-04-12 /pmc/articles/PMC10144301/ /pubmed/37110645 http://dx.doi.org/10.3390/molecules28083408 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hua, Yi Song, Mingxia Guo, Qiaoyue Luo, Yiqin Deng, Xianqing Huang, Yushan Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title | Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title_full | Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title_fullStr | Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title_full_unstemmed | Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title_short | Antiseizure Properties of Histamine H(3) Receptor Antagonists Belonging 3,4-Dihydroquinolin-2(1H)-Ones |
title_sort | antiseizure properties of histamine h(3) receptor antagonists belonging 3,4-dihydroquinolin-2(1h)-ones |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144301/ https://www.ncbi.nlm.nih.gov/pubmed/37110645 http://dx.doi.org/10.3390/molecules28083408 |
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