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Use of half-generation PAMAM dendrimers (G0. 5–G3. 5) with carboxylate end-groups to improve the DACHPtCl2 and 5-FU efficacy as anticancer drugs

2021Journal article Open access
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dc.contributor.authorCamacho, Cláudia
dc.contributor.authorTomás, Helena
dc.contributor.authorRodrigues, João
dc.date.accessioned2022-02-17T09:03:59Z
dc.date.available2022-02-17T09:03:59Z
dc.date.issued2021
dc.description.abstractThe DACHPtCl2 compound (trans-(R,R)-1,2-diaminocyclohexanedichloroplatinum(II)) is a potent anticancer drug with a broad spectrum of activity and is less toxic than oxaliplatin (trans-l-diaminocyclohexane oxalate platinum II), with which it shares the active metal fragment DACHPt. Nevertheless, due to poor water solubility, its use as a chemotherapeutic drug is limited. Here, DACHPtCl2 was conjugated, in a bidentate form, with half-generation PAMAM dendrimers (G0.5–G3.5) with carboxylate end-groups, and the resulting conjugates were evaluated against various types of cancer cell lines. In this way, we aimed at increasing the solubility and availability at the target site of DACHPt while potentially reducing the adverse side effects. DNA binding assays showed a hyperchromic effect compatible with DNA helix’s disruption upon the interaction of the metallodendrimers and/or the released active metallic fragments with DNA. Furthermore, the prepared DACHPt metallodendrimers presented cytotoxicity in a wide set of cancer cell lines used (the relative potency regarding oxaliplatin was in general high) and were not hemotoxic. Importantly, their selectivity for A2780 and CACO-2 cancer cells with respect to non-cancer cells was particularly high. Subsequently, the anticancer drug 5-FU was loaded in a selected metallodendrimer (the G2.5COO(DACHPt)16) to investigate a possible synergistic effect between the two drugs carried by the same dendrimer scaffold and tested for cytotoxicity in A2780cisR and CACO-2 cancer cell lines. This combination resulted in IC50 values much lower than the IC50 for 5-FU but higher than those found for the metallodendrimers without 5-FU. It seems, thus, that the metallic fragment-induced cytotoxicity dominates over the cytotoxicity of 5-FU in the set of considered cell lines.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCamacho, C., Tomás, H., & Rodrigues, J. (2021). Use of half-generation PAMAM dendrimers (G0. 5–G3. 5) with carboxylate end-groups to improve the DACHPtCl2 and 5-FU efficacy as anticancer drugs. Molecules, 26(10), 2924. https://doi.org/10.3390/molecules26102924pt_PT
dc.identifier.doi10.3390/molecules26102924pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/4086
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationMadeira Chemistry Research Centre
dc.relationMadeira Chemistry Research Centre
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDendrimerspt_PT
dc.subjectPAMAMpt_PT
dc.subjectAnticancer drugspt_PT
dc.subjectMetallodrugspt_PT
dc.subjectOxaliplatinpt_PT
dc.subject5-FUpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titleUse of half-generation PAMAM dendrimers (G0. 5–G3. 5) with carboxylate end-groups to improve the DACHPtCl2 and 5-FU efficacy as anticancer drugspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMadeira Chemistry Research Centre
oaire.awardTitleMadeira Chemistry Research Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00674%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00674%2F2020/PT
oaire.citation.issue10pt_PT
oaire.citation.startPage2924pt_PT
oaire.citation.titleMoleculespt_PT
oaire.citation.volume26pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameCamacho
person.familyNameTomás
person.familyNameRodrigues
person.givenNameCláudia Sofia
person.givenNameHelena
person.givenNameJoão
person.identifier556975
person.identifier.ciencia-id6C1E-7D62-56D1
person.identifier.ciencia-id4D14-D31E-A8BE
person.identifier.ciencia-idA81C-620E-DD6A
person.identifier.orcid0000-0002-7856-2041
person.identifier.orcid0000-0003-4552-1953
person.identifier.ridE-5991-2010
person.identifier.ridB-6816-2008
person.identifier.scopus-author-id6508104177
person.identifier.scopus-author-id9233278800
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.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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