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Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells

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dc.contributor.authorRivas, Feriannys
dc.contributor.authorMedeiros, Andrea
dc.contributor.authorComini, Marcelo
dc.contributor.authorSuescun, Leopoldo
dc.contributor.authorRodríguez Arce, Esteban
dc.contributor.authorMartins, Marta
dc.contributor.authorPinheiro, Teresa
dc.contributor.authorMarques, Fernanda
dc.contributor.authorGambino, Dinorah
dc.date.accessioned2022-04-18T15:29:11Z
dc.date.available2022-04-18T15:29:11Z
dc.date.issued2019
dc.description© 2019 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractSearching for a more effective chemotherapy for the treatment of Human African trypanosomiasis, the disease caused by the parasite Trypanosoma brucei, and cancer, in the current work five new [PtII(L)(dppf)](PF6) compounds, with HL = 8-hydroxyquinoline derivatives and dppf = 1,1'-bis(diphenylphosphino)ferrocene, were synthesized and fully characterized. Crystal structures of three compounds were solved by XRD. The compounds displayed fairly good activity against bloodstream T. brucei, with IC50 values in the submicromolar range (IC50: 0.14-0.93 μM), and good selectivity towards the pathogen (SI: 11 - 48) with respect to mammalian macrophages (cell line J774). Coordination to the {Pt-dppf} moiety led, in most cases, to an enhancement of the activity in respect to the bioactive ligands (11 to 41 fold). Cytotoxicity was assessed against wildtype (A2780) and cisplatin-resistance (A2780cisR) ovarian cancer cell lines. Four [PtII(L)(dppf)](PF6) compounds were more active (IC50: 1.2-4.4 μM) than cisplatin (IC50: 26.0 μM) on A2780 cells and showed far superior activity than the reference drug against A2780cisR cells. Platinum levels in A2780 cells showed poor correlation between cellular uptake and the cytotoxic activity. All the complexes interacted with DNA and the most active ones induced reactive oxygen species (ROS) formation which suggested that the mechanism of action for these complexes may be mediated by oxidative stress and interaction with DNA that could act as a potential molecular target for this type of complexes. Some complexes of this series could be considered new hits for the development of prospective agents against trypanosomatid parasites and ovarian cancer.pt_PT
dc.description.sponsorshipF.R. and E.R.A. acknowledge the support of the Agencia Nacional de Investigación e Innovación (ANII, Uruguay) through the grants POS_NAC_2016_1_129899 and POS_NAC_2018_1_151206 and POS_NAC_2015_1_110215, respectively. This work was supported by PEDECIBA Uruguay. M.A.C. acknowledges the support of ANII (grant PR_FMV_2009_1_2617) and FOCEM (MERCOSUR Structural Convergence Fund, COF 03/11). F.M. and T.P. acknowledge the support of the Fundação para a Ciência e a Tecnologia (contracts UID/MULTI/04349/2013 and UID/BIO/04565/2013) and LISBOA-01-0145-FEDER-007317.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Inorg Biochem. 2019 Oct;199:110779pt_PT
dc.identifier.doi10.1016/j.jinorgbio.2019.110779pt_PT
dc.identifier.eissn1873-3344
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10451/52403
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationLISBOA-01-0145-FEDER-007317pt_PT
dc.relationCentre for Nuclear Sciences and Technologies
dc.relationInstitute for Bioengineering and Biosciences
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/journal-of-inorganic-biochemistrypt_PT
dc.subjectAnti-proliferativept_PT
dc.subjectCancer cellspt_PT
dc.subjectFerrocenyl compoundspt_PT
dc.subjectHydroxyquinoline derivativespt_PT
dc.subjectPlatinumpt_PT
dc.subjectTrypanosoma bruceipt_PT
dc.titlePt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Nuclear Sciences and Technologies
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04349%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04565%2F2013/PT
oaire.citation.titleJournal of Inorganic Biochemistrypt_PT
oaire.citation.volume199pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameMartins
person.familyNamePinheiro
person.givenNameMarta
person.givenNameTeresa
person.identifier.ciencia-id0B17-EB4A-5073
person.identifier.orcid0000-0003-0429-9380
person.identifier.orcid0000-0002-1836-2603
person.identifier.ridO-8984-2019
person.identifier.scopus-author-id55268246400
person.identifier.scopus-author-id35596784200
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.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication94b5d31a-3a49-4277-aeab-86497a45fde8
relation.isAuthorOfPublication7c81fca1-a3b5-4095-ac9e-925ce981bda4
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