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.coauthor | Ribeiro, Nadia | |
dc.contributor.coauthor | Bulut, Ipek | |
dc.contributor.coauthor | Teixeira, Carlos | |
dc.contributor.coauthor | Yildizhan, Yasemin | |
dc.contributor.coauthor | Andre, Vania | |
dc.contributor.coauthor | Adao, Pedro | |
dc.contributor.coauthor | Pessoa, Joao Costa | |
dc.contributor.coauthor | Correia, Isabel | |
dc.contributor.department | Animal Laboratory | |
dc.contributor.department | School of Medicine | |
dc.contributor.kuauthor | Ayhan, Ceyda Açılan | |
dc.contributor.kuauthor | Cevatemre, Buse | |
dc.contributor.schoolcollegeinstitute | Laboratory | |
dc.contributor.schoolcollegeinstitute | SCHOOL OF MEDICINE | |
dc.date.accessioned | 2024-11-09T23:06:18Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Four 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.indexedby | WOS | |
dc.description.indexedby | Scopus | |
dc.description.issue | 1 | |
dc.description.openaccess | NO | |
dc.description.publisherscope | International | |
dc.description.sponsoredbyTubitakEu | N/A | |
dc.description.sponsorship | Fundacao para a Ciencia e Tecnologia (FCT) [UIDB/00100/2020] | |
dc.description.sponsorship | FCT [SFRH/BD/135797/2018, UID/MAR/04292/2019, UIDB/04292/2020] | |
dc.description.sponsorship | FCT Investigator [IF/00841/2012] | |
dc.description.sponsorship | project "SmartBioR- Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate" - Centro 2020 [Centro-01-0145-FEDER-000018] | |
dc.description.sponsorship | Portugal 2020 | |
dc.description.sponsorship | European Regional Development Fund (FEDER) | |
dc.description.sponsorship | Koc University School of Medicine (KUSOM) | |
dc.description.sponsorship | Presidency of Turkey | |
dc.description.sponsorship | Presidency 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.sponsorship | Fundação 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.volume | 50 | |
dc.identifier.doi | 10.1039/d0dt03331f | |
dc.identifier.eissn | 1477-9234 | |
dc.identifier.issn | 1477-9226 | |
dc.identifier.quartile | Q1 | |
dc.identifier.scopus | 2-s2.0-85098956008 | |
dc.identifier.uri | https://doi.org/10.1039/d0dt03331f | |
dc.identifier.uri | https://hdl.handle.net/20.500.14288/8958 | |
dc.identifier.wos | 605666100017 | |
dc.keywords | Reduced schiff-bases | |
dc.keywords | Aromatic O-Hydroxyaldehydes | |
dc.keywords | Copper(Ii) Complexes | |
dc.keywords | Dna-binding | |
dc.keywords | Crystal-structures | |
dc.keywords | Catecholase activity | |
dc.keywords | Cleavage activity | |
dc.keywords | Cancer-cells | |
dc.keywords | Donor atoms | |
dc.keywords | Amino-acids | |
dc.language.iso | eng | |
dc.publisher | Royal Soc Chemistry | |
dc.relation.ispartof | Dalton Transactions | |
dc.subject | Chemistry | |
dc.subject | Inorganic nuclear | |
dc.title | Cu(II) and V(IV)O complexes with tri- or tetradentate ligands based on (2-hydroxybenzyl)-L-alanines reveal promising anticancer therapeutic potential | |
dc.type | Journal Article | |
dspace.entity.type | Publication | |
local.contributor.kuauthor | Cevatemre, Buse | |
local.contributor.kuauthor | Ayhan, Ceyda Açılan | |
local.publication.orgunit1 | SCHOOL OF MEDICINE | |
local.publication.orgunit1 | Laboratory | |
local.publication.orgunit2 | Animal Laboratory | |
local.publication.orgunit2 | School of Medicine | |
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