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Synthesis, anticonvulsant, and antinociceptive activity of new 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides
anticonvulsant activity
antinociceptive activity
pyrrolidine-2,5-dione
amides
The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3- (2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug-valproic acid (68.30mg/kg vs. 252.74mg/kg in theMES test and 28.20mg/kg vs. 130.64mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds-namely, 6 and 19-was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltagegated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.
cris.lastimport.scopus | 2024-04-07T17:48:11Z | |
cris.lastimport.wos | 2024-04-09T23:14:30Z | |
dc.abstract.en | The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3- (2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug-valproic acid (68.30mg/kg vs. 252.74mg/kg in theMES test and 28.20mg/kg vs. 130.64mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds-namely, 6 and 19-was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltagegated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect. | pl |
dc.affiliation | Wydział Farmaceutyczny : Zakład Farmakodynamiki | pl |
dc.affiliation | Wydział Farmaceutyczny : Zakład Biochemii Farmaceutycznej | pl |
dc.affiliation | Wydział Farmaceutyczny : Zakład Chemii Leków | pl |
dc.cm.date | 2021-05-15 | |
dc.cm.id | 103936 | |
dc.contributor.author | Góra, Małgorzata | pl |
dc.contributor.author | Czopek, Anna - 129115 | pl |
dc.contributor.author | Rapacz, Anna - 133263 | pl |
dc.contributor.author | Gębska, Anna - 129492 | pl |
dc.contributor.author | Wójcik-Pszczoła, Katarzyna - 104230 | pl |
dc.contributor.author | Pękala, Elżbieta - 133125 | pl |
dc.contributor.author | Kamiński, Krzysztof - 129989 | pl |
dc.date.accession | 2021-04-29 | pl |
dc.date.accessioned | 2021-05-15T10:06:49Z | |
dc.date.available | 2021-05-15T10:06:49Z | |
dc.date.issued | 2021 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.number | 6 | pl |
dc.description.points | 100 | |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 26 | pl |
dc.identifier.articleid | 1564 | pl |
dc.identifier.doi | 10.3390/molecules26061564 | pl |
dc.identifier.eissn | 1420-3049 | pl |
dc.identifier.project | ROD UJ / OP | pl |
dc.identifier.uri | https://ruj.uj.edu.pl/xmlui/handle/item/271335 | |
dc.identifier.weblink | https://www.mdpi.com/1420-3049/26/6/1564 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.relation.uri | * | |
dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | * |
dc.rights.licence | CC-BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | * |
dc.share.type | otwarte czasopismo | |
dc.subject.en | anticonvulsant activity | pl |
dc.subject.en | antinociceptive activity | pl |
dc.subject.en | pyrrolidine-2,5-dione | pl |
dc.subject.en | amides | pl |
dc.subtype | Article | pl |
dc.title | Synthesis, anticonvulsant, and antinociceptive activity of new 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides | pl |
dc.title.journal | Molecules | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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