Repository logo
 
Publication

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

2019-09Journal article Restricted access
Simple item page
dc.contributor.authorMatos, Cristina P.
dc.contributor.authorAddis, Yemataw
dc.contributor.authorNunes, Patrique
dc.contributor.authorBarroso, Sonia
dc.contributor.authorAlho, Irina
dc.contributor.authorMartins, Marta
dc.contributor.authorMatos, Antonio P. A.
dc.contributor.authorMarques, Fernanda
dc.contributor.authorCavaco, Isabel
dc.contributor.authorPessoa, Joao Costa
dc.contributor.authorCorreia, Isabel
dc.date.accessioned2020-07-24T10:51:46Z
dc.date.available2020-07-24T10:51:46Z
dc.date.issued2019-09
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 mu M) towards ovarian cells, showing IC50 values 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)(NNI(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 activationells incubated with EZn(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.
dc.description.sponsorshipFundagao para a Cioncia e Tecnologia (FCT) [UID/QUI/00100/2013, UID/MULTI/04349/2013, UlD/B10/04565/2013, RECl/QEQ-QIN/0189/2012, RECl/QEQ-MED/0330/2012]
dc.description.sponsorshipPrograma Operacional Regional de Lisboa [LISBOA-01-0145-FEDER-007317]
dc.description.sponsorshipIsabel Correia thanks program Investigador FCT [IF/00841/2012]
dc.description.sponsorshipFCTPortuguese Foundation for Science and Technology [SFRH/BD/101214/2014, SFRH/BD/108743/2015, SFRH/BPD/7394/2010]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.jinorgbio.2019.110727
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10400.1/14267
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.subjectN-Salicylideneglycinato complexes
dc.subjectDna-binding
dc.subjectZinc(Ii) complexes
dc.subjectPolypyridyl complexes
dc.subjectCopper(Ii) complexes
dc.subjectAnticancer activity
dc.subjectCrystal-structures
dc.subjectCellular uptake
dc.subjectNucleic-acid
dc.subject1,10-Phenanthroline
dc.titleExploring the cytotoxic activity of new phenanthroline salicylaldimine Zn(II) complexes
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.citation.startPageUNSP 110727
oaire.citation.titleJournal of Inorganic Biochemistry
oaire.citation.volume198
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNamePALMA ANTUNES CAVACO
person.givenNameISABEL MARIA
person.identifierH-9087-2012
person.identifier.ciencia-idD515-FB5E-1205
person.identifier.orcid0000-0001-8651-9054
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
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationb499959b-bea5-4292-bdb2-4311b0aa82de
relation.isAuthorOfPublication.latestForDiscoveryb499959b-bea5-4292-bdb2-4311b0aa82de
relation.isProjectOfPublication9afed05e-58cb-478e-acc7-625439f9c745
relation.isProjectOfPublication28685ae5-8021-47a9-948e-d3532f171e8c
relation.isProjectOfPublication.latestForDiscovery28685ae5-8021-47a9-948e-d3532f171e8c

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
1-s2.0-S016201341930090X-main.pdf
Size:
2.78 MB
Format:
Adobe Portable Document Format
Download

Collections

FCT2-Artigos (em revistas ou actas indexadas)