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

Detalhes bibliográficos
Autor(a) principal: Camacho, Cláudia
Data de Publicação: 2021
Outros Autores: Tomás, Helena, Rodrigues, João
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.13/4086
Resumo: The 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.
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spelling Use of half-generation PAMAM dendrimers (G0. 5–G3. 5) with carboxylate end-groups to improve the DACHPtCl2 and 5-FU efficacy as anticancer drugsDendrimersPAMAMAnticancer drugsMetallodrugsOxaliplatin5-FU.Faculdade de Ciências Exatas e da EngenhariaCentro de Química da MadeiraThe 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.MDPIDigitUMaCamacho, CláudiaTomás, HelenaRodrigues, João2022-02-17T09:03:59Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/4086engCamacho, 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/molecules2610292410.3390/molecules26102924info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-24T05:11:47Zoai:digituma.uma.pt:10400.13/4086Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-03-24T05:11:47Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv 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
title 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
spellingShingle 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
Camacho, Cláudia
Dendrimers
PAMAM
Anticancer drugs
Metallodrugs
Oxaliplatin
5-FU
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author Camacho, Cláudia
author_facet Camacho, Cláudia
Tomás, Helena
Rodrigues, João
author_role author
author2 Tomás, Helena
Rodrigues, João
author2_role author
author
dc.contributor.none.fl_str_mv DigitUMa
dc.contributor.author.fl_str_mv Camacho, Cláudia
Tomás, Helena
Rodrigues, João
dc.subject.por.fl_str_mv Dendrimers
PAMAM
Anticancer drugs
Metallodrugs
Oxaliplatin
5-FU
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
topic Dendrimers
PAMAM
Anticancer drugs
Metallodrugs
Oxaliplatin
5-FU
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
description The 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2022-02-17T09:03:59Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.13/4086
url http://hdl.handle.net/10400.13/4086
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Camacho, 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/molecules26102924
10.3390/molecules26102924
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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