In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives

Metabolic stability, mutagenicity, antimutagenicity, and the ability to scavenge free radicals of four novel 8-methoxy-purine-2,6-dione derivatives (compounds 1¿4) demonstrating analgesic and anti-inflammatory properties were determined. Metabolic stability was evaluated in Cunninghamella and micros...

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Autores: Marć, Małgorzata Anna, Domínguez-Álvarez, Enrique, Sloczynska, K., Zmudzki, P., Chlon-Rzepa, G., Pekala, E.
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/169932
Acesso em linha:http://hdl.handle.net/10261/169932
Access Level:acceso abierto
Palavra-chave:Ames test
Cunninghamella assay
DPPH assay
Microsomal stability
Alternative test
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spelling In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione DerivativesMarć, Małgorzata AnnaDomínguez-Álvarez, EnriqueSloczynska, K.Zmudzki, P.Chlon-Rzepa, G.Pekala, E.Ames testCunninghamella assayDPPH assayMicrosomal stabilityAlternative testMetabolic stability, mutagenicity, antimutagenicity, and the ability to scavenge free radicals of four novel 8-methoxy-purine-2,6-dione derivatives (compounds 1¿4) demonstrating analgesic and anti-inflammatory properties were determined. Metabolic stability was evaluated in Cunninghamella and microsomal models, mutagenic and antimutagenic properties were assessed using the Ames and the Vibrio harveyi tests, and free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. In the Cunninghamella model, compound 2 did not undergo any biotransformation; whereas 3 and 4 showed less metabolic stability: 1¿9 and 53¿88% of the parental compound, respectively, underwent biotransformation reactions in different Cunninghamella strains. The metabolites detected after the biotransformation of 3 and 4 were aromatic hydroxylation and N-dealkylation products. On the other hand, the N-dealkylation product was the only metabolite formed in microsome assay. Additionally, these derivatives do not possess mutagenic potential in microbiological models (Vibrio harveyi and Salmonella typhimurium) considered. Moreover, all compounds showed a strong chemopreventive activity in the modified Vibrio harveyi strains BB7X and BB7M. However, radical scavenging activity was not the mechanism which explained the observed chemopreventive activity.This work was supported by Jagiellonian University Medical College under Grants K/DSC/002885 and K/ZDS/005488.Peer ReviewedSpringer NatureConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2018201820182018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/169932reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1007/s12010-017-2527-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1699322026-05-22T06:33:51Z
dc.title.none.fl_str_mv In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
title In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
spellingShingle In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
Marć, Małgorzata Anna
Ames test
Cunninghamella assay
DPPH assay
Microsomal stability
Alternative test
title_short In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
title_full In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
title_fullStr In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
title_full_unstemmed In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
title_sort In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives
dc.creator.none.fl_str_mv Marć, Małgorzata Anna
Domínguez-Álvarez, Enrique
Sloczynska, K.
Zmudzki, P.
Chlon-Rzepa, G.
Pekala, E.
author Marć, Małgorzata Anna
author_facet Marć, Małgorzata Anna
Domínguez-Álvarez, Enrique
Sloczynska, K.
Zmudzki, P.
Chlon-Rzepa, G.
Pekala, E.
author_role author
author2 Domínguez-Álvarez, Enrique
Sloczynska, K.
Zmudzki, P.
Chlon-Rzepa, G.
Pekala, E.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Ames test
Cunninghamella assay
DPPH assay
Microsomal stability
Alternative test
topic Ames test
Cunninghamella assay
DPPH assay
Microsomal stability
Alternative test
description Metabolic stability, mutagenicity, antimutagenicity, and the ability to scavenge free radicals of four novel 8-methoxy-purine-2,6-dione derivatives (compounds 1¿4) demonstrating analgesic and anti-inflammatory properties were determined. Metabolic stability was evaluated in Cunninghamella and microsomal models, mutagenic and antimutagenic properties were assessed using the Ames and the Vibrio harveyi tests, and free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. In the Cunninghamella model, compound 2 did not undergo any biotransformation; whereas 3 and 4 showed less metabolic stability: 1¿9 and 53¿88% of the parental compound, respectively, underwent biotransformation reactions in different Cunninghamella strains. The metabolites detected after the biotransformation of 3 and 4 were aromatic hydroxylation and N-dealkylation products. On the other hand, the N-dealkylation product was the only metabolite formed in microsome assay. Additionally, these derivatives do not possess mutagenic potential in microbiological models (Vibrio harveyi and Salmonella typhimurium) considered. Moreover, all compounds showed a strong chemopreventive activity in the modified Vibrio harveyi strains BB7X and BB7M. However, radical scavenging activity was not the mechanism which explained the observed chemopreventive activity.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/169932
url http://hdl.handle.net/10261/169932
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1007/s12010-017-2527-z
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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