Publicação
Exploitation of new chromene-based compounds as promising agents for cancer treatment
| Resumo: | Cancer is a devastating disease, responsible for 9.9 million deaths worldwide in 2020. Female breast cancer is the most diagnosed cancer and with the highest mortality rate. The statistics show that this tendency will continue to rise in the next years, becoming urgent the development of new and more effective drugs capable to overcome resistance and toxicity problems, associated to the current available therapies. The chromene moiety has been recognized in several natural and synthetic compounds, exhibiting very interesting biological activities, namely anticancer activity. The present work aimed to assess the anticancer potential of two synthesized chromene-based family – FD and DL-chromene-based compounds, in the breast cancer cell model. The anticancer potential of the FD-chromene-based compounds was evaluated through a first screening of the compounds in different BC cell lines. Chromenes displaying the best activity profile proceeded to IC50 determination and in vitro and in vivo toxicity assays, using a non-neoplastic cell line (MCF-10A) and the Caenorhabditis elegans model, proving their non-toxic profile. To study their mechanism of action, more specific in vitro assays were conducted and the results showed the ability of the compounds to induce cell death through apoptosis, cell cycle arrest, to inhibit cell migration, proliferation and to interfere with key enzymes in the glycolytic process. Lastly, two lead compounds were identified and the Chick Chorioallantoic Membrane (CAM) model was used for in vivo efficacy studies. The analyzed chromenes were able to inhibit tumor proliferation and angiogenesis, evidencing their potential as anticancer drug candidates. The anticancer potential regarding DL-chromene-based compounds was initiated in a previous project. In the present work, three of the most promising molecules were selected to investigate their influence in the expression levels of proteins related to cell death and metabolism, to characterize their mechanism of action. The results showed that the chromenes were able to induce cell death through apoptosis as well as to reduce the expression levels of multiple key enzymes involved in the glycolytic process. |
|---|---|
| Autores principais: | Carvalho, Ana Luísa Queirós |
| Assunto: | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866876210957516800 |
|---|---|
| author | Carvalho, Ana Luísa Queirós |
| author_facet | Carvalho, Ana Luísa Queirós |
| author_role | author |
| contributor_name_str_mv | Costa, Marta Sílvia Freitas Proença, M. Fernanda R. P. Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Carvalho, Ana Luísa Queirós\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Costa, Marta Sílvia Freitas Proença, M. Fernanda R. P. Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Carvalho, Ana Luísa Queirós |
| datacite.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-11-11T09:29:46Z |
| datacite.date.embargoed.fl_str_mv | 2022-11-11T09:29:46Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| datacite.titles.title.fl_str_mv | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| dc.contributor.none.fl_str_mv | Costa, Marta Sílvia Freitas Proença, M. Fernanda R. P. Universidade do Minho |
| dc.creator.none.fl_str_mv | Carvalho, Ana Luísa Queirós |
| dc.date.Accepted.fl_str_mv | 2021-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-11-11T09:29:46Z |
| dc.date.embargoed.fl_str_mv | 2022-11-11T09:29:46Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/80588 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| dc.title.fl_str_mv | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_bdcc |
| description | Cancer is a devastating disease, responsible for 9.9 million deaths worldwide in 2020. Female breast cancer is the most diagnosed cancer and with the highest mortality rate. The statistics show that this tendency will continue to rise in the next years, becoming urgent the development of new and more effective drugs capable to overcome resistance and toxicity problems, associated to the current available therapies. The chromene moiety has been recognized in several natural and synthetic compounds, exhibiting very interesting biological activities, namely anticancer activity. The present work aimed to assess the anticancer potential of two synthesized chromene-based family – FD and DL-chromene-based compounds, in the breast cancer cell model. The anticancer potential of the FD-chromene-based compounds was evaluated through a first screening of the compounds in different BC cell lines. Chromenes displaying the best activity profile proceeded to IC50 determination and in vitro and in vivo toxicity assays, using a non-neoplastic cell line (MCF-10A) and the Caenorhabditis elegans model, proving their non-toxic profile. To study their mechanism of action, more specific in vitro assays were conducted and the results showed the ability of the compounds to induce cell death through apoptosis, cell cycle arrest, to inhibit cell migration, proliferation and to interfere with key enzymes in the glycolytic process. Lastly, two lead compounds were identified and the Chick Chorioallantoic Membrane (CAM) model was used for in vivo efficacy studies. The analyzed chromenes were able to inhibit tumor proliferation and angiogenesis, evidencing their potential as anticancer drug candidates. The anticancer potential regarding DL-chromene-based compounds was initiated in a previous project. In the present work, three of the most promising molecules were selected to investigate their influence in the expression levels of proteins related to cell death and metabolism, to characterize their mechanism of action. The results showed that the chromenes were able to induce cell death through apoptosis as well as to reduce the expression levels of multiple key enzymes involved in the glycolytic process. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/f7704e10-9a0e-4bd5-b50e-563b7d3d50b3/download |
| id | rum_fa3f1d38dbbb00c9730cb3f9bcbbaa49 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/80588 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/80588 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Carvalho, Ana Luísa Queirós |
| publishDate | 2021 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporCancer is a devastating disease, responsible for 9.9 million deaths worldwide in 2020. Female breast cancer is the most diagnosed cancer and with the highest mortality rate. The statistics show that this tendency will continue to rise in the next years, becoming urgent the development of new and more effective drugs capable to overcome resistance and toxicity problems, associated to the current available therapies. The chromene moiety has been recognized in several natural and synthetic compounds, exhibiting very interesting biological activities, namely anticancer activity. The present work aimed to assess the anticancer potential of two synthesized chromene-based family – FD and DL-chromene-based compounds, in the breast cancer cell model. The anticancer potential of the FD-chromene-based compounds was evaluated through a first screening of the compounds in different BC cell lines. Chromenes displaying the best activity profile proceeded to IC50 determination and in vitro and in vivo toxicity assays, using a non-neoplastic cell line (MCF-10A) and the Caenorhabditis elegans model, proving their non-toxic profile. To study their mechanism of action, more specific in vitro assays were conducted and the results showed the ability of the compounds to induce cell death through apoptosis, cell cycle arrest, to inhibit cell migration, proliferation and to interfere with key enzymes in the glycolytic process. Lastly, two lead compounds were identified and the Chick Chorioallantoic Membrane (CAM) model was used for in vivo efficacy studies. The analyzed chromenes were able to inhibit tumor proliferation and angiogenesis, evidencing their potential as anticancer drug candidates. The anticancer potential regarding DL-chromene-based compounds was initiated in a previous project. In the present work, three of the most promising molecules were selected to investigate their influence in the expression levels of proteins related to cell death and metabolism, to characterize their mechanism of action. The results showed that the chromenes were able to induce cell death through apoptosis as well as to reduce the expression levels of multiple key enzymes involved in the glycolytic process.application/pdfporExploitation of new chromene-based compounds as promising agents for cancer treatmentCarvalho, Ana Luísa QueirósCosta, Marta Sílvia FreitasProença, M. Fernanda R. P.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:2029904272022-11-11T09:29:46Z202120212021-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/80588http://purl.org/coar/access_right/c_abf2open accessCancerBreast cancerChromenesLead compoundCancroCancro da mamaCromenosCompostos lead6021755 bytesliteraturehttp://purl.org/coar/resource_type/c_bdccmaster thesis2021http://creativecommons.org/licenses/by-nc-nd/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/f7704e10-9a0e-4bd5-b50e-563b7d3d50b3/download |
| spellingShingle | Exploitation of new chromene-based compounds as promising agents for cancer treatment Carvalho, Ana Luísa Queirós Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| status | SINGLETON |
| subject.fl_str_mv | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| title | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| title_full | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| title_fullStr | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| title_full_unstemmed | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| title_short | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| title_sort | Exploitation of new chromene-based compounds as promising agents for cancer treatment |
| topic | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| topic_facet | Cancer Breast cancer Chromenes Lead compound Cancro Cancro da mama Cromenos Compostos lead |
| url | https://hdl.handle.net/1822/80588 |
| visible | 1 |