Repository logo
 
Publication

Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents

2018Journal article Restricted access
Simple item page
dc.contributor.authorFigueiredo, Joana
dc.contributor.authorSerrano, João L.
dc.contributor.authorCavalheiro, Eunice Cerdeira Soares
dc.contributor.authorKeurulainen, Leena Maria
dc.contributor.authorYli-Kauhaluoma, Jari Tapani
dc.contributor.authorMoreira, Vânia M
dc.contributor.authorFerreira, Susana
dc.contributor.authorDomingues, F.C.
dc.contributor.authorSilvestre, Samuel
dc.contributor.authorAlmeida, Paulo
dc.date.accessioned2020-01-29T12:07:12Z
dc.date.available2020-01-29T12:07:12Z
dc.date.issued2018
dc.description.abstractBarbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC50 = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejmech.2017.11.070pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/8883
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier Massonpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S022352341730973X?via%3Dihubpt_PT
dc.subjectBarbituratespt_PT
dc.subjectXanthine oxidase inhibitionpt_PT
dc.subjectAntioxidantpt_PT
dc.subjectAntibacterialpt_PT
dc.subjectCytotoxicitypt_PT
dc.titleTrisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agentspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F00709%2F2013/PT
oaire.citation.endPage842pt_PT
oaire.citation.startPage829pt_PT
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume143pt_PT
oaire.fundingStream5876
person.familyNameRodrigues Figueiredo
person.familyNameKeurulainen
person.familyNameYli-Kauhaluoma
person.familyNameMoreira
person.familyNameFerreira
person.familyNameDomingues
person.familyNameSilvestre
person.familyNameAlmeida
person.givenNameJoana Patrícia
person.givenNameLeena Maria
person.givenNameJari
person.givenNameVânia
person.givenNameSusana
person.givenNameFernanda
person.givenNameSamuel
person.givenNamePaulo
person.identifier.ciencia-id5C1D-F8C1-505C
person.identifier.ciencia-id981F-DD99-F0B7
person.identifier.ciencia-idF718-3569-E911
person.identifier.ciencia-id6514-0498-3E8F
person.identifier.ciencia-id4711-9D77-F772
person.identifier.ciencia-id6E18-3C6F-6842
person.identifier.orcid0000-0002-4711-107X
person.identifier.orcid0000-0001-8528-7757
person.identifier.orcid0000-0003-0370-7653
person.identifier.orcid0000-0001-6169-5035
person.identifier.orcid0000-0001-8308-2862
person.identifier.orcid0000-0002-9540-0853
person.identifier.orcid0000-0003-4297-5108
person.identifier.orcid0000-0003-0110-4795
person.identifier.ridC-8237-2013
person.identifier.ridA-6810-2016
person.identifier.ridN-7295-2013
person.identifier.ridA-4822-2017
person.identifier.ridA-1600-2014
person.identifier.scopus-author-id35510530700
person.identifier.scopus-author-id55791001100
person.identifier.scopus-author-id34874668400
person.identifier.scopus-author-id10139481400
person.identifier.scopus-author-id8234535800
person.identifier.scopus-author-id7102848111
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication40262a11-1bc4-43dd-8145-04761dbbd122
relation.isAuthorOfPublication690a32bc-6958-4516-854a-b1c16e27b8c4
relation.isAuthorOfPublication3d49b4b5-bf30-4160-855c-71178a92eedf
relation.isAuthorOfPublicatione6f9e044-3554-4473-9975-53d8ac85d3d4
relation.isAuthorOfPublication9f4d39d4-7d9c-4c17-8a8a-523d32d4de20
relation.isAuthorOfPublication8d5fe6e2-21af-4557-9c46-84103254a18a
relation.isAuthorOfPublicationcbc08fd7-daea-4c58-8538-796f17946523
relation.isAuthorOfPublicationd29c61c1-9269-464b-b820-baa2ccc0f95f
relation.isAuthorOfPublication.latestForDiscovery9f4d39d4-7d9c-4c17-8a8a-523d32d4de20
relation.isProjectOfPublicationcb4688cf-40da-4197-9eb0-c55bad699ad3
relation.isProjectOfPublication.latestForDiscoverycb4688cf-40da-4197-9eb0-c55bad699ad3

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
2018. Trisubstituted barbiturates and thiobarbiturates- Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents.pdf
Size:
1.18 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

ICI - CICS | Documentos por Auto-Depósito
FC - DQ | Documentos por Auto-Depósito