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Half-sandwich Ru(p-cymene) compounds with diphosphanes: In Vitro and In Vivo evaluation as potential anticancer metallodrugs

2021-02-11Journal article Restricted access
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dc.contributor.authorLenis Rojas, Oscar
dc.contributor.authorRobalo, M. Paula
dc.contributor.authorTomaz, Ana Isabel
dc.contributor.authorFernandes, Alexandra
dc.contributor.authorRoma-Rodrigues, Catarina
dc.contributor.authorGonçalves Teixeira, Ricardo
dc.contributor.authorMarques, Fernanda
dc.contributor.authorFOLGUEIRA, MONICA
dc.contributor.authorYáñez, Julián
dc.contributor.authorAlba-González, Anabel
dc.contributor.authorSalamini-Montemurri, Martin
dc.contributor.authorPech-Puch, Dawrin
dc.contributor.authorVázquez-García, Digna
dc.contributor.authorLópez-Torres, Margarita
dc.contributor.authorFernandez, Alberto
dc.contributor.authorFernandez, Jesus J.
dc.date.accessioned2021-04-27T11:26:35Z
dc.date.available2021-04-27T11:26:35Z
dc.date.issued2021-02-11
dc.description.abstractRuthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(p-cymene)(L)Cl]-[CF3SO3] (L = 1,1-bis(methylenediphenylphosphano)ethylene, 1; L = 1,1-bis(diphenylphosphano)ethylene, 2), which were characterized by elemental analysis, mass spectrometry, H-1 and P-31{H-1} NMR, UV-vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex 1 exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC50 values in the MCF7 cancer cells, complexes 1 and 2 presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of 1 and 2 in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that in vitro a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes 1 and 2 both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex 1 (the most toxic of the two) exhibited a lethal toxicity LC50 value about 1 order of magnitude higher than any IC50 concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLENIS-ROJAS, Oscar A.; [et al] – Half-sandwich Ru(p-cymene) compounds with diphosphanes: In Vitro and In Vivo evaluation as potential anticancer metallodrugs. Inorganic Chemistry. ISSN 0020-1669. Vol. 60, N.º 5 (2021), pp. 2914-2930pt_PT
dc.identifier.doi10.1021/acs.inorgchem.0c02768pt_PT
dc.identifier.eissn1520-510X
dc.identifier.issn0020-1669
dc.identifier.urihttp://hdl.handle.net/10400.21/13233
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Chemical Societypt_PT
dc.relationED431C 2018/39 - Xunta de Galicia (Galicia, Spain) under the Grupos de Referencia Competitiva Programmept_PT
dc.relationPEst 2015-2020 - FCTpt_PT
dc.relationUIDB/QUI/00100/2020 - FCTpt_PT
dc.relationUID/Multi/04378/2020 - Applied Molecular Biosciences Unit -UCIBIO - FCT/MCTESpt_PT
dc.relationSFRH/BD/135830/2018 - FCT European Commissionpt_PT
dc.relationCA18202 - COST Action NECTAR (European Cooperation in Science and Technology)pt_PT
dc.relationLISBOA-01-0145-FEDER-007660 - FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI)pt_PT
dc.relation.publisherversionhttps://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.0c02768pt_PT
dc.subjectHalf-sandwich rutheniumpt_PT
dc.subjectHuman tumor cellspt_PT
dc.subjectOvarian (A2780)pt_PT
dc.subjectBreast (MCF7 and MDA-MB-231)pt_PT
dc.subjectReactive oxygen species (ROS)pt_PT
dc.subjectApoptosis and autophagypt_PT
dc.titleHalf-sandwich Ru(p-cymene) compounds with diphosphanes: In Vitro and In Vivo evaluation as potential anticancer metallodrugspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04349%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FQEQ-QIN%2F0189%2F2012/PT
oaire.citation.endPage2930pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage2914pt_PT
oaire.citation.titleInorganic Chemistrypt_PT
oaire.citation.volume60pt_PT
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person.familyNameLenis Rojas
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person.givenNameJulián
person.givenNameAnabel
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person.givenNameMargarita
person.givenNameJesús José
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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.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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