Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes

We report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of ben...

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Autores: Ribeiro, Nádia|||0000-0003-2725-7781, Bulut, Ipek, Sergi, Baris, Pósa, Vivien, Spengler, Gabriella, Sciortino, Giuseppe|||0000-0001-9657-1788, André, Vânia, Ferreira, Liliana P., Biver, Tarita, Ugone, Valeria|||0000-0002-2830-3869, Garribba, Eugenio|||0000-0002-7229-5966, Costa Pessoa, João|||0000-0002-3978-9964, Enyedy, Éva A.|||0000-0002-8058-8128, Acilan, Ceyda, Correia, Isabel|||0000-0001-7096-4284
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:288741
Acceso en línea:https://ddd.uab.cat/record/288741
https://dx.doi.org/urn:doi:10.3389/fchem.2023.1106349
Access Level:acceso abierto
Palabra clave:8-hydoxyquinoline
Antibacterial
Anticancer
Copper complexes
Schiff bases
Speciation
SDG 3 - Good Health and Well-being
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spelling Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexesRibeiro, Nádia|||0000-0003-2725-7781Bulut, IpekSergi, BarisPósa, VivienSpengler, GabriellaSciortino, Giuseppe|||0000-0001-9657-1788André, VâniaFerreira, Liliana P.Biver, TaritaUgone, Valeria|||0000-0002-2830-3869Garribba, Eugenio|||0000-0002-7229-5966Costa Pessoa, João|||0000-0002-3978-9964Enyedy, Éva A.|||0000-0002-8058-8128Acilan, CeydaCorreia, Isabel|||0000-0001-7096-42848-hydoxyquinolineAntibacterialAnticancerCopper complexesSchiff basesSpeciationSDG 3 - Good Health and Well-beingWe report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (1-8) are either formulated as [Cu(HL)acetate] (with L1 and L4) or as [Cu(Ln)]3 (n = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L5 and [Cu(L5)]3, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v/v) DMSO/H2O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH-1)] for L = L1, L5 and L6, and also [Cu(LH-2)] for L = L6, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L1, L5 and L6 are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395 mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L1, L3, L5 and L7, and of the corresponding complexes with calf thymus DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds 1, 3, 5, and 8 were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, 8 emerges as the most promising one, presenting low IC50 values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/288741https://dx.doi.org/urn:doi:10.3389/fchem.2023.1106349reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FJC2019-039135-Iopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2887412026-06-06T12:50:31Z
dc.title.none.fl_str_mv Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
title Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
spellingShingle Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
Ribeiro, Nádia|||0000-0003-2725-7781
8-hydoxyquinoline
Antibacterial
Anticancer
Copper complexes
Schiff bases
Speciation
SDG 3 - Good Health and Well-being
title_short Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
title_full Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
title_fullStr Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
title_full_unstemmed Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
title_sort Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes
dc.creator.none.fl_str_mv Ribeiro, Nádia|||0000-0003-2725-7781
Bulut, Ipek
Sergi, Baris
Pósa, Vivien
Spengler, Gabriella
Sciortino, Giuseppe|||0000-0001-9657-1788
André, Vânia
Ferreira, Liliana P.
Biver, Tarita
Ugone, Valeria|||0000-0002-2830-3869
Garribba, Eugenio|||0000-0002-7229-5966
Costa Pessoa, João|||0000-0002-3978-9964
Enyedy, Éva A.|||0000-0002-8058-8128
Acilan, Ceyda
Correia, Isabel|||0000-0001-7096-4284
author Ribeiro, Nádia|||0000-0003-2725-7781
author_facet Ribeiro, Nádia|||0000-0003-2725-7781
Bulut, Ipek
Sergi, Baris
Pósa, Vivien
Spengler, Gabriella
Sciortino, Giuseppe|||0000-0001-9657-1788
André, Vânia
Ferreira, Liliana P.
Biver, Tarita
Ugone, Valeria|||0000-0002-2830-3869
Garribba, Eugenio|||0000-0002-7229-5966
Costa Pessoa, João|||0000-0002-3978-9964
Enyedy, Éva A.|||0000-0002-8058-8128
Acilan, Ceyda
Correia, Isabel|||0000-0001-7096-4284
author_role author
author2 Bulut, Ipek
Sergi, Baris
Pósa, Vivien
Spengler, Gabriella
Sciortino, Giuseppe|||0000-0001-9657-1788
André, Vânia
Ferreira, Liliana P.
Biver, Tarita
Ugone, Valeria|||0000-0002-2830-3869
Garribba, Eugenio|||0000-0002-7229-5966
Costa Pessoa, João|||0000-0002-3978-9964
Enyedy, Éva A.|||0000-0002-8058-8128
Acilan, Ceyda
Correia, Isabel|||0000-0001-7096-4284
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 8-hydoxyquinoline
Antibacterial
Anticancer
Copper complexes
Schiff bases
Speciation
SDG 3 - Good Health and Well-being
topic 8-hydoxyquinoline
Antibacterial
Anticancer
Copper complexes
Schiff bases
Speciation
SDG 3 - Good Health and Well-being
description We report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (1-8) are either formulated as [Cu(HL)acetate] (with L1 and L4) or as [Cu(Ln)]3 (n = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L5 and [Cu(L5)]3, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v/v) DMSO/H2O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH-1)] for L = L1, L5 and L6, and also [Cu(LH-2)] for L = L6, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L1, L5 and L6 are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395 mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L1, L3, L5 and L7, and of the corresponding complexes with calf thymus DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds 1, 3, 5, and 8 were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, 8 emerges as the most promising one, presenting low IC50 values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/288741
https://dx.doi.org/urn:doi:10.3389/fchem.2023.1106349
url https://ddd.uab.cat/record/288741
https://dx.doi.org/urn:doi:10.3389/fchem.2023.1106349
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 FJC2019-039135-I
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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