Logo do repositório
 
Publicação

Exploring the cytotoxic activity of new phenanthroline salicylaldimine Zn(II) complexes

2019Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorMatos, Cristina
dc.contributor.authorAddis, Yemataw
dc.contributor.authorNunes, Patrique
dc.contributor.authorBarroso, Sónia
dc.contributor.authorAlho, Irina
dc.contributor.authorMartins, Marta
dc.contributor.authorMatos, António P.A.
dc.contributor.authorMarques, Fernanda
dc.contributor.authorCavaco, Isabel
dc.contributor.authorPessoa, João
dc.contributor.authorCorreia, Isabel
dc.date.accessioned2022-01-11T16:49:46Z
dc.date.available2022-01-11T16:49:46Z
dc.date.issued2019
dc.description© 2019 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractZinc(II) complexes bearing N-salicylideneglycinate (Sal-Gly) and 1,10-phenanthroline (phen) or phenanthroline derivatives [NN = 5-chloro-1,10-phenanthroline, 5-amine-1,10-phenanthroline (amphen), 4,7-diphenyl-1,10-phenanthroline (Bphen) and 5,6-epoxy-5,6-dihydro-1,10-phenanthroline] are synthesized. Complexes formulated as [Zn(NN)2(H2O)2]2+(NN = phen and amphen), are also prepared. The cytotoxicity of the compounds is evaluated towards a panel of human cancer cells: ovarian (A2780), breast (MCF7) and cervical (HeLa), as well as non-tumoral V79 fibroblasts. All compounds display higher cytotoxicity than cisplatin (IC50 = 22.5 ± 5.0 μM) towards ovarian cells, showing IC50values in the low micromolar range. Overall, all compounds show higher selectivity for the A2780 cells than for the non-tumoral cells and higher selectivity indexes (IC50(V79)/IC50(A2780) than cisplatin. [Zn(Sal-Gly)(NN)(H2O)] complexes induce caspase-dependent apoptosis in A2780 cells, except [Zn(Sal-Gly)(Bphen)(H2O)], one of the most cytotoxic of the series. The cellular uptake in the ovarian cells analyzed by Inductively Coupled Plasma mass spectrometry indicates different Zn distribution profiles. Transmission electronic microscopy shows mitochondria alterations and apoptotic features consistent with caspase activation; cells incubated with [Zn(Sal-Gly)(amphen)(H2O)] present additional nuclear membrane alterations in agreement with significant association with the nucleus. The increase of reactive oxygen species and lipid peroxidation forms could be related to apoptosis induction. [Zn(NN)2(H2O)2]2+complexes have high ability to bind DNA through intercalation/groove binding, and circular dichroism data suggests that the main type of species that interact with DNA is [Zn(NN)]2+. Studies varying the % of fetal bovine serum (1-15%) in cell media show that albumin binding decreases the complex activity, indicating that distinct speciation of Zn- and phen-containing species in cell media may affect the cytotoxicity.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (FCT) (projects UID/QUI/00100/2013, UID/MULTI/04349/2013, UID/BIO/04565/2013, RECI/QEQ-QIN/0189/2012, RECI/QEQ-MED/0330/2012), Programa Operacional Regional de Lisboa (LISBOA-01-0145-FEDER-007317). Isabel Correia thanks program Investigador FCT (IF/00841/2012), Cristina Matos, Patrique Nunes and Sónia Barroso thank FCT for grants SFRH/BD/101214/2014, SFRH/BD/108743/2015 and SFRH/BPD/7394/2010, respectively.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Inorg Biochem. 2019 Sep;198:110727pt_PT
dc.identifier.doi10.1016/j.jinorgbio.2019.110727pt_PT
dc.identifier.eissn1873-3344
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10451/50778
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationLISBOA-01-0145-FEDER-007317pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/journal-of-inorganic-biochemistrypt_PT
dc.subjectAnticancer activitypt_PT
dc.subjectLipid peroxidespt_PT
dc.subjectPolypyridyl ligandspt_PT
dc.subjectROSpt_PT
dc.subjectSalicylaldiminespt_PT
dc.subjectZinc(II) complexespt_PT
dc.titleExploring the cytotoxic activity of new phenanthroline salicylaldimine Zn(II) complexespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00100%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04349%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIO%2F04565%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FQEQ-QIN%2F0189%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FQEQ-MED%2F0330%2F2012/PT
oaire.citation.titleJournal of Inorganic Biochemistrypt_PT
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
person.familyNamePereira de Matos
person.familyNameNunes
person.familyNameDuarte
person.familyNameMartins
person.familyNameMarujo Marques
person.familyNamePALMA ANTUNES CAVACO
person.familyNameCosta Pessoa
person.familyNameCorreia
person.givenNameCristina
person.givenNamePatrique
person.givenNameIrina
person.givenNameMarta
person.givenNameFernanda
person.givenNameISABEL MARIA
person.givenNameJoão
person.givenNameIsabel
person.identifierA-3413-2011
person.identifierJ-9790-2013
person.identifierH-9087-2012
person.identifierH-9078-2012
person.identifier.ciencia-idD416-909B-5131
person.identifier.ciencia-id651D-2E22-AB73
person.identifier.ciencia-id1C11-A0C7-418A
person.identifier.ciencia-idD515-FB5E-1205
person.identifier.ciencia-id9D14-9F80-868C
person.identifier.ciencia-id1719-285A-843B
person.identifier.orcid0000-0002-0171-8829
person.identifier.orcid0000-0003-1693-1267
person.identifier.orcid0000-0002-3190-7479
person.identifier.orcid0000-0003-0429-9380
person.identifier.orcid0000-0001-8440-5299
person.identifier.orcid0000-0001-8651-9054
person.identifier.orcid0000-0002-3978-9964
person.identifier.orcid0000-0001-7096-4284
person.identifier.ridH-7772-2012
person.identifier.scopus-author-id56002785300
person.identifier.scopus-author-id55268246400
person.identifier.scopus-author-id16402591700
person.identifier.scopus-author-id7003557498
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication937f5fbb-3596-48a8-8f98-01602c386865
relation.isAuthorOfPublicatione90161c0-df01-406b-822e-392420a82a5f
relation.isAuthorOfPublicationac30657e-6e0f-4437-8aea-bb1bcf05e1c5
relation.isAuthorOfPublication94b5d31a-3a49-4277-aeab-86497a45fde8
relation.isAuthorOfPublicationf8526a84-8c6b-4ab4-8dd8-e9a66ecc043c
relation.isAuthorOfPublicationc92df699-8012-4d1a-94a4-d9002098a691
relation.isAuthorOfPublicationccbe5dba-1b25-4a7c-8078-3e99ec16d382
relation.isAuthorOfPublication5918480b-dc55-4cc6-9b72-d53503665eb1
relation.isAuthorOfPublication.latestForDiscovery5918480b-dc55-4cc6-9b72-d53503665eb1
relation.isProjectOfPublication49c294b3-79f3-4715-9895-d6a3297ec860
relation.isProjectOfPublication7088e8f8-de9d-425e-aebe-98eafc065dc8
relation.isProjectOfPublication6ba8dfe4-a799-4168-8e48-91830bf4d780
relation.isProjectOfPublication83962804-b368-4736-9731-ec26e37ba209
relation.isProjectOfPublicationa264008d-824f-46c4-bfca-1f2aa128c92e
relation.isProjectOfPublication.latestForDiscovery7088e8f8-de9d-425e-aebe-98eafc065dc8

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
Exploring_cytotoxic.pdf
Tamanho:
2.78 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais