Publication:
Cu(II) and V(IV)O complexes with tri- or tetradentate ligands based on (2-hydroxybenzyl)-L-alanines reveal promising anticancer therapeutic potential

dc.contributor.coauthorRibeiro, Nadia
dc.contributor.coauthorBulut, Ipek
dc.contributor.coauthorTeixeira, Carlos
dc.contributor.coauthorYildizhan, Yasemin
dc.contributor.coauthorAndre, Vania
dc.contributor.coauthorAdao, Pedro
dc.contributor.coauthorPessoa, Joao Costa
dc.contributor.coauthorCorreia, Isabel
dc.contributor.departmentAnimal Laboratory
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorAyhan, Ceyda Açılan
dc.contributor.kuauthorCevatemre, Buse
dc.contributor.schoolcollegeinstituteLaboratory
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:06:18Z
dc.date.issued2021
dc.description.abstractFour new ligand precursors (H2L1-H2L4), derived from the Mannich condensation of two amino acids (L-Val and L-Phe) and two 3,5-disubstituted phenols (t-Bu or Me), and the corresponding oxidovanadium(IV) (1-4) and copper(II) (6-7) complexes are synthesized. Two other related compounds (H2L5 and H2L6), containing an additional 2-methyl-pyridine arm, and the corresponding (VO)-O-IV (5) and Cu-II (8-9) complexes were also obtained. All metal complexes are monomeric in the solid state, having a solvent molecule or a chloride ion in the coordination sphere. The in vitro cytotoxic activity of all compounds is evaluated against cancer cells from different origins. The IC50 values at 72 h are in the range of 6-15 mu M for HeLa cells, 4-17 mu M for A-549 cells and >25 mu M for MDA-MB-231 cells, except for [(VOL1)-O-IV(CH3OH)] (1) and [CuL6(H2O)] (9). With the exception of H2L6, overall, the metal complexes are more cytotoxic than the corresponding ligand precursors. Globally, the cellular viability data show that (i) the L-Phe derived compounds are more cytotoxic than the corresponding L-Val complexes; (ii) the presence of the bulkier t-Bu groups increases the cytotoxicity; (iii) the presence of a 2-methyl-pyridine arm increases considerably the cytotoxicity; and (iv) the Cu-II-complexes are more cytotoxic than the (VO)-O-IV-compounds. Complexes [(VOL3)-O-IV(CH3OH)] (3), [CuL3(H2O)] (7) and [CuL5(H2O)] (8) were further evaluated and their mechanism of action was determined to be apoptosis, evidenced by AnnexinV staining and the increase in caspase 3/7 activity. Compounds 3, 7 and 8 also exhibit DNA cleavage activity, involving the formation of reactive oxygen species and were able to induce genomic damage in cells as determined by COMET assay.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.issue1
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipFundacao para a Ciencia e Tecnologia (FCT) [UIDB/00100/2020]
dc.description.sponsorshipFCT [SFRH/BD/135797/2018, UID/MAR/04292/2019, UIDB/04292/2020]
dc.description.sponsorshipFCT Investigator [IF/00841/2012]
dc.description.sponsorshipproject "SmartBioR- Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate" - Centro 2020 [Centro-01-0145-FEDER-000018]
dc.description.sponsorshipPortugal 2020
dc.description.sponsorshipEuropean Regional Development Fund (FEDER)
dc.description.sponsorshipKoc University School of Medicine (KUSOM)
dc.description.sponsorshipPresidency of Turkey
dc.description.sponsorshipPresidency of Strategy and Budget
dc.description.sponsorship[SFRH/BPD/79778/2011]
dc.description.sponsorship[BL/CQE-2014-001]
dc.description.sponsorship[PD/BD/106078/2015]
dc.description.sponsorshipFundação para a Ciência e a Tecnologia [PD/BD/106078/2015, SFRH/BD/135797/2018] Funding Source: FCT The authors thank the financial support from Fundacao para a Ciencia e Tecnologia (FCT) through project UIDB/00100/2020. N. Ribeiro acknowledges FCT for SFRH/BD/135797/2018 grant. C. Teixeira and P. AdAo acknowledge grants SFRH/BPD/79778/2011, BL/CQE-2014-001 and PD/BD/106078/2015. Isabel Correia thanks program FCT Investigator (IF/00841/2012). P. AdAo also acknowledges the MARE - Centro de Ciencias do Mar e do Ambiente, Politecnico de Leiria, which is financed by national funds from FCT (UID/MAR/04292/2019, UIDB/04292/2020) and the project "SmartBioR- Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate" (Centro-01-0145-FEDER-000018) co-funded by Centro 2020, Portugal 2020 and European Regional Development Fund (FEDER). The Portuguese NMR and Mass spectrometry IST-UL are acknowledged for the access to the equipment.r This work was supported by Koc University School of Medicine (KUSOM) and the authors gratefully acknowledge use of the services and facilities of the Koc University Research Center for Translational Medicine (KUTTAM), funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.
dc.description.volume50
dc.identifier.doi10.1039/d0dt03331f
dc.identifier.eissn1477-9234
dc.identifier.issn1477-9226
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-85098956008
dc.identifier.urihttps://doi.org/10.1039/d0dt03331f
dc.identifier.urihttps://hdl.handle.net/20.500.14288/8958
dc.identifier.wos605666100017
dc.keywordsReduced schiff-bases
dc.keywordsAromatic O-Hydroxyaldehydes
dc.keywordsCopper(Ii) Complexes
dc.keywordsDna-binding
dc.keywordsCrystal-structures
dc.keywordsCatecholase activity
dc.keywordsCleavage activity
dc.keywordsCancer-cells
dc.keywordsDonor atoms
dc.keywordsAmino-acids
dc.language.isoeng
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofDalton Transactions
dc.subjectChemistry
dc.subjectInorganic nuclear
dc.titleCu(II) and V(IV)O complexes with tri- or tetradentate ligands based on (2-hydroxybenzyl)-L-alanines reveal promising anticancer therapeutic potential
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorCevatemre, Buse
local.contributor.kuauthorAyhan, Ceyda Açılan
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Laboratory
local.publication.orgunit2Animal Laboratory
local.publication.orgunit2School of Medicine
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relation.isParentOrgUnitOfPublication.latestForDiscovery20385dee-35e7-484b-8da6-ddcc08271d96

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