Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.22/16394 |
Resumo: | Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation. |
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Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome FormulationsCarbonatesTumor Cell LinesCell ProliferationDrug CarriersGliomaGlucoseGlycosylationHumansLiposomesSilver CompoundsXanthonesNanotechnologyProliposomesFollowing our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation.This work was partially supported through national funds provided by FCT and European Regional Development Fund (ERDF) through the COMPETE—Programa Operacional Factores de Competitividade (POFC) programme, under the project PTDC/MAR-BIO/4694/2014 (POCI-01-0145-FEDER-016790 and Project 3599-PPCDT) in the framework of the programme PT2020MDPIRepositório Científico do Instituto Politécnico do PortoAlves, AnaCorreia-da-Silva, MartaNunes, ClaúdiaCampos, JoãoSousa, EmíliaSilva, PatríciaBousbaa, HassanRodrigues, FranciscaFerreira, DomingosCosta, PauloPinto, Madalena2020-10-30T14:57:30Z2019-012019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/16394eng10.3390/molecules24030409info: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:RCAAP2023-03-13T13:02:40Zoai:recipp.ipp.pt:10400.22/16394Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:35:51.512475Repositório 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 |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
title |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
spellingShingle |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations Alves, Ana Carbonates Tumor Cell Lines Cell Proliferation Drug Carriers Glioma Glucose Glycosylation Humans Liposomes Silver Compounds Xanthones Nanotechnology Proliposomes |
title_short |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
title_full |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
title_fullStr |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
title_full_unstemmed |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
title_sort |
Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations |
author |
Alves, Ana |
author_facet |
Alves, Ana Correia-da-Silva, Marta Nunes, Claúdia Campos, João Sousa, Emília Silva, Patrícia Bousbaa, Hassan Rodrigues, Francisca Ferreira, Domingos Costa, Paulo Pinto, Madalena |
author_role |
author |
author2 |
Correia-da-Silva, Marta Nunes, Claúdia Campos, João Sousa, Emília Silva, Patrícia Bousbaa, Hassan Rodrigues, Francisca Ferreira, Domingos Costa, Paulo Pinto, Madalena |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Alves, Ana Correia-da-Silva, Marta Nunes, Claúdia Campos, João Sousa, Emília Silva, Patrícia Bousbaa, Hassan Rodrigues, Francisca Ferreira, Domingos Costa, Paulo Pinto, Madalena |
dc.subject.por.fl_str_mv |
Carbonates Tumor Cell Lines Cell Proliferation Drug Carriers Glioma Glucose Glycosylation Humans Liposomes Silver Compounds Xanthones Nanotechnology Proliposomes |
topic |
Carbonates Tumor Cell Lines Cell Proliferation Drug Carriers Glioma Glucose Glycosylation Humans Liposomes Silver Compounds Xanthones Nanotechnology Proliposomes |
description |
Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-01 2019-01-01T00:00:00Z 2020-10-30T14:57:30Z |
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/10400.22/16394 |
url |
http://hdl.handle.net/10400.22/16394 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.3390/molecules24030409 |
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 |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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