Publicação
Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones
| Resumo: | Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC50 values lower than 10 μM. These findings suggest that the substitution pattern of the xanthone scaffold modulated the inhibitory activity of these compounds, and some structure–activity relationships could be established for both assays. In addition, the type of inhibition was also studied, and the results indicate a competitive type of inhibition for α-amylase activity by xanthones 2c, 3b, 3c and γ-mangostin (6). On the other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1–6 against α-glucosidase. The present work can open a promising area of research based on the design of novel xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism and therefore in the management of type 2 diabetes mellitus. |
|---|---|
| Autores principais: | Santos, Clementina M.M. |
| Outros Autores: | Proença, Carina; Freitas, Marisa; Araújo, Alberto N.; Silva, Artur; Fernandes, Eduarda |
| Assunto: | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Bragança |
| Idioma: | inglês |
| Origem: | Biblioteca Digital do IPB |
| _version_ | 1867173001962717184 |
|---|---|
| author | Santos, Clementina M.M. |
| author2 | Proença, Carina Freitas, Marisa Araújo, Alberto N. Silva, Artur Fernandes, Eduarda |
| author2_role | author author author author author |
| author_facet | Santos, Clementina M.M. Proença, Carina Freitas, Marisa Araújo, Alberto N. Silva, Artur Fernandes, Eduarda |
| author_role | author |
| contributor_name_str_mv | Biblioteca Digital do IPB |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Santos, Clementina M.M.\",\"Person.identifier.orcid\":\"0000-0003-4380-7990\"},{\"Person.name\":\"Proença, Carina\"},{\"Person.name\":\"Freitas, Marisa\"},{\"Person.name\":\"Araújo, Alberto N.\"},{\"Person.name\":\"Silva, Artur\"},{\"Person.name\":\"Fernandes, Eduarda\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Biblioteca Digital do IPB |
| datacite.creators.creator.creatorName.fl_str_mv | Santos, Clementina M.M. Proença, Carina Freitas, Marisa Araújo, Alberto N. Silva, Artur Fernandes, Eduarda |
| datacite.date.Accepted.fl_str_mv | 2022-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-09-01T09:10:35Z |
| datacite.date.embargoed.fl_str_mv | 2022-09-01T09:10:35Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| datacite.titles.title.fl_str_mv | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| dc.contributor.none.fl_str_mv | Biblioteca Digital do IPB |
| dc.creator.none.fl_str_mv | Santos, Clementina M.M. Proença, Carina Freitas, Marisa Araújo, Alberto N. Silva, Artur Fernandes, Eduarda |
| dc.date.Accepted.fl_str_mv | 2022-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-09-01T09:10:35Z |
| dc.date.embargoed.fl_str_mv | 2022-09-01T09:10:35Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10198/25862 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | The Royal Society of Chemistry |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| dc.title.fl_str_mv | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC50 values lower than 10 μM. These findings suggest that the substitution pattern of the xanthone scaffold modulated the inhibitory activity of these compounds, and some structure–activity relationships could be established for both assays. In addition, the type of inhibition was also studied, and the results indicate a competitive type of inhibition for α-amylase activity by xanthones 2c, 3b, 3c and γ-mangostin (6). On the other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1–6 against α-glucosidase. The present work can open a promising area of research based on the design of novel xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism and therefore in the management of type 2 diabetes mellitus. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://bibliotecadigital.ipb.pt/bitstreams/88bd5d25-900b-4a22-ad38-ad0934669a38/download |
| funding.funder.alternateName_str_mv | FCT FCT FCT FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | 6817 - DCRRNI ID 6817 - DCRRNI ID 3599-PPCDT 9471 - RIDTI CEEC IND 3ed |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10198/25862 |
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| institution | Instituto Politécnico de Bragança |
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| language | eng |
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| oai_identifier_str | oai:bibliotecadigital.ipb.pt:10198/25862 |
| organization_str_mv | urn:organizationAcronym:ipb |
| person_str_mv | Santos, Clementina M.M. Santos, Clementina M.M. https://www.ciencia-id.pt/9018-DB9C-C590 9018-DB9C-C590 http://orcid.org/0000-0003-4380-7990 0000-0003-4380-7990 Proença, Carina Freitas, Marisa Araújo, Alberto N. Silva, Artur Fernandes, Eduarda |
| publishDate | 2022 |
| publisher.none.fl_str_mv | The Royal Society of Chemistry |
| reponame_str | Biblioteca Digital do IPB |
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| spelling | engThe Royal Society of Chemistrypt_PTXanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC50 values lower than 10 μM. These findings suggest that the substitution pattern of the xanthone scaffold modulated the inhibitory activity of these compounds, and some structure–activity relationships could be established for both assays. In addition, the type of inhibition was also studied, and the results indicate a competitive type of inhibition for α-amylase activity by xanthones 2c, 3b, 3c and γ-mangostin (6). On the other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1–6 against α-glucosidase. The present work can open a promising area of research based on the design of novel xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism and therefore in the management of type 2 diabetes mellitus.application/pdfpt_PTInhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthonesPersonalSantos, Clementina M.M.DSpacehttp://dspace.org/items/64f662b6-775d-4ea0-bfd7-f527af0ac1a0DSpacehttp://dspace.org/items/64f662b6-775d-4ea0-bfd7-f527af0ac1a0SantosClementina M.M.Ciência IDhttps://www.ciencia-id.pt9018-DB9C-C590ORCIDhttp://orcid.org0000-0003-4380-7990Scopus Author IDhttps://www.scopus.com7201458663Proença, CarinaFreitas, MarisaAraújo, Alberto N.Silva, ArturFernandes, EduardaHostingInstitutionOrganizationalBiblioteca Digital do IPBe-mailmailto:dspace@ipb.ptdspace@ipb.ptISSNIsPartOf2042-6496DOIIsPartOf10.1039/D2FO00023G2022-09-01T09:10:35Z20222022-01-01T00:00:00ZHandlehttp://hdl.handle.net/10198/25862http://purl.org/coar/access_right/c_abf2open accessDiabetesXanthoneAmylaseGlucosidaseMangiferinMangostinInhibitionSAR1339596 bytesFundação para a Ciência e a TecnologiaMountain Research Center6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaAssociated Laboratory for Green Chemistry - Clean Technologies and Processes6817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaScreening and pharmacological characterization of flavonoids as lead compounds for obesity treatment3599-PPCDTCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaDevelopment of new inhibitors of invasive osteosarcoma based on fisetin derivatives9471 - RIDTICrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaNanoencapsulation of polyphenols as a novel approach to treat Diabetes mellitusCEEC IND 3edCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal article2022http://creativecommons.org/licenses/by/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/88bd5d25-900b-4a22-ad38-ad0934669a38/downloadFood & Function131479307941 |
| spellingShingle | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones Santos, Clementina M.M. Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| status | SINGLETON |
| subject.fl_str_mv | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| title | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| title_full | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| title_fullStr | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| title_full_unstemmed | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| title_short | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| title_sort | Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones |
| topic | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| topic_facet | Diabetes Xanthone Amylase Glucosidase Mangiferin Mangostin Inhibition SAR |
| url | http://hdl.handle.net/10198/25862 |
| visible | 1 |