Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis...

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Autores principales:	Ewelina Kozioł, Krzysztof Jóźwiak, Barbara Budzyńska, Peter A. M. de Witte, Daniëlle Copmans, Krystyna Skalicka-Woźniak
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	coumarins zebrafish epilepsy pentylenetetrazole behavior electrophysiology Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/bfb8209bb7054d04901b47510445b657
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spelling	oai:doaj.org-article:bfb8209bb7054d04901b47510445b6572021-11-11T16:53:27ZComparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish10.3390/ijms2221114201422-00671661-6596https://doaj.org/article/bfb8209bb7054d04901b47510445b6572021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11420https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.Ewelina KoziołKrzysztof JóźwiakBarbara BudzyńskaPeter A. M. de WitteDaniëlle CopmansKrystyna Skalicka-WoźniakMDPI AGarticlecoumarinszebrafishepilepsypentylenetetrazolebehaviorelectrophysiologyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11420, p 11420 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	coumarins zebrafish epilepsy pentylenetetrazole behavior electrophysiology Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	coumarins zebrafish epilepsy pentylenetetrazole behavior electrophysiology Biology (General) QH301-705.5 Chemistry QD1-999 Ewelina Kozioł Krzysztof Jóźwiak Barbara Budzyńska Peter A. M. de Witte Daniëlle Copmans Krystyna Skalicka-Woźniak Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
description	Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.
format	article
author	Ewelina Kozioł Krzysztof Jóźwiak Barbara Budzyńska Peter A. M. de Witte Daniëlle Copmans Krystyna Skalicka-Woźniak
author_facet	Ewelina Kozioł Krzysztof Jóźwiak Barbara Budzyńska Peter A. M. de Witte Daniëlle Copmans Krystyna Skalicka-Woźniak
author_sort	Ewelina Kozioł
title	Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
title_short	Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
title_full	Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
title_fullStr	Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
title_full_unstemmed	Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish
title_sort	comparative antiseizure analysis of diverse natural coumarin derivatives in zebrafish
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bfb8209bb7054d04901b47510445b657
work_keys_str_mv	AT ewelinakozioł comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish AT krzysztofjozwiak comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish AT barbarabudzynska comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish AT peteramdewitte comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish AT daniellecopmans comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish AT krystynaskalickawozniak comparativeantiseizureanalysisofdiversenaturalcoumarinderivativesinzebrafish
_version_	1718432263197163520

Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

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