Cargando…
1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy
There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178883/ https://www.ncbi.nlm.nih.gov/pubmed/32253957 http://dx.doi.org/10.1080/14756366.2020.1748026 |
_version_ | 1783525558926180352 |
---|---|
author | Kaproń, Barbara Czarnomysy, Robert Wysokiński, Mariusz Andrys, Rudolf Musilek, Kamil Angeli, Andrea Supuran, Claudiu T. Plech, Tomasz |
author_facet | Kaproń, Barbara Czarnomysy, Robert Wysokiński, Mariusz Andrys, Rudolf Musilek, Kamil Angeli, Andrea Supuran, Claudiu T. Plech, Tomasz |
author_sort | Kaproń, Barbara |
collection | PubMed |
description | There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects. |
format | Online Article Text |
id | pubmed-7178883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-71788832020-05-01 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy Kaproń, Barbara Czarnomysy, Robert Wysokiński, Mariusz Andrys, Rudolf Musilek, Kamil Angeli, Andrea Supuran, Claudiu T. Plech, Tomasz J Enzyme Inhib Med Chem Research Paper There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects. Taylor & Francis 2020-04-07 /pmc/articles/PMC7178883/ /pubmed/32253957 http://dx.doi.org/10.1080/14756366.2020.1748026 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Kaproń, Barbara Czarnomysy, Robert Wysokiński, Mariusz Andrys, Rudolf Musilek, Kamil Angeli, Andrea Supuran, Claudiu T. Plech, Tomasz 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title | 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title_full | 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title_fullStr | 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title_full_unstemmed | 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title_short | 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy |
title_sort | 1,2,4-triazole-based anticonvulsant agents with additional ros scavenging activity are effective in a model of pharmacoresistant epilepsy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178883/ https://www.ncbi.nlm.nih.gov/pubmed/32253957 http://dx.doi.org/10.1080/14756366.2020.1748026 |
work_keys_str_mv | AT kapronbarbara 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT czarnomysyrobert 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT wysokinskimariusz 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT andrysrudolf 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT musilekkamil 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT angeliandrea 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT supuranclaudiut 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy AT plechtomasz 124triazolebasedanticonvulsantagentswithadditionalrosscavengingactivityareeffectiveinamodelofpharmacoresistantepilepsy |