Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: design, synthesis and molecular modeling

Full metadata record
DC FieldValueLanguage
dc.contributorLEDS - Laboratório de Dor e Sinalizaçãopt_BR
dc.contributor.authorPereira, Gustavo José Vascopt_BR
dc.contributor.authorTavares, Maurício Temotheopt_BR
dc.contributor.authorAzevedo, Ricardo Alexandre dept_BR
dc.contributor.authorMartins, Barbara Behrpt_BR
dc.contributor.authorCunha, Micael Rodriguespt_BR
dc.contributor.authorBhardwaj, Rajeshpt_BR
dc.contributor.authorCury, Yarapt_BR
dc.contributor.authorZambelli, Vanessa Olzonpt_BR
dc.contributor.authorBarbosa, Euzébio Guimarãespt_BR
dc.contributor.authorHediger, Matthias A.pt_BR
dc.contributor.authorParise-Filho, Robertopt_BR
dc.date.accessioned2020-07-09T21:24:17Z-
dc.date.available2020-07-09T21:24:17Z-
dc.date.issued2019pt_BR
dc.identifier.citationPereira GJV, Tavares MT, Azevedo RA, Martins BB, Cunha MR, Bhardwaj R, et al. Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: design, synthesis and molecular modeling. Bioorg. Med. Chem.. 2019 Jul;27(13):2893-2904. doi:10.1016/j.bmc.2019.05.020.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2771-
dc.description.abstractThe use of molecules inspired by natural scaffolds has proven to be a very promising and efficient method of drug discovery. In this work, capsaicin, a natural product from Capsicum peppers with antitumor properties, was used as a prototype to obtain urea and thiourea analogues. Among the most promising compounds, the thiourea compound 6g exhibited significant cytotoxic activity against human melanoma A2058 cells that was twice as high as that of capsaicin. Compound 6g induced significant and dose-dependent G0/G1 cell cycle arrest in A2058 cells triggering cell death by apoptosis. Our results suggest that 6g modulates the RAF/MEK/ERK pathway, inducing important morphological changes, such as formation of apoptotic bodies and increased levels of cleaved caspase-3. Compared to capsaicin, 6g had no significant TRPV1/6 agonist effect or irritant effects on mice. Molecular modeling studies corroborate the biological findings and suggest that 6g, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. Inverse virtual screening strategy found MEK1 as a possible biological target for 6g. Consistent with these findings, our observations suggested that 6g could be developed as a potential anticancer agent.pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipSwiss National Science Foundation (SNSF)pt_BR
dc.description.sponsorshipThe State Secretariat for Education, Research and Innovation (SERI)pt_BR
dc.format.extentp. 2893-2904pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofBioorganic & Medicinal Chemistrypt_BR
dc.titleCapsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: design, synthesis and molecular modelingpt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1016/j.bmc.2019.05.020pt_BR
dc.identifier.urlhttps://doi.org/10.1016/j.bmc.2019.05.020pt_BR
dc.contributor.externalUniversidade de São Paulo (USP)¦¦Brasilpt_BR
dc.contributor.externalUniversity of Bern¦¦Suíçapt_BR
dc.contributor.externalUniversidade Federal do Rio Grande do Norte (UFRN)¦¦Brasilpt_BR
dc.identifier.citationvolume27pt_BR
dc.identifier.citationissue13pt_BR
dc.subject.keywordPepperspt_BR
dc.subject.keywordAnticancer agentspt_BR
dc.subject.keywordDrug designpt_BR
dc.subject.keywordNatural productpt_BR
dc.subject.keywordCapsaicinpt_BR
dc.subject.keywordUreapt_BR
dc.subject.keywordThioureapt_BR
dc.subject.keywordCancerpt_BR
dc.subject.keywordChemotherapypt_BR
dc.subject.keywordApoptosispt_BR
dc.relation.ispartofabbreviatedBioorg Med Chempt_BR
dc.identifier.citationabntv. 27, n. 13, p. 2893-2904, jul. 2019pt_BR
dc.identifier.citationvancouver2019 Jul;27(13):2893-2904pt_BR
dc.contributor.butantanZambelli, Vanessa Olzon|:Pesquisador:Docente Permanente PPGTOX|:LEDS - Laboratório de Dor e Sinalização|:pt_BR
dc.contributor.butantanMartins, Barbara Behr|:Aluno|:LEDS - Laboratório de Dor e Sinalização|:pt_BR
dc.contributor.butantanCury, Yara|:Aluno|:LEDS - Laboratório de Dor e Sinalização|:pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/19311-6pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2017/00689-0pt_BR
dc.sponsorship.butantanSwiss National Science Foundation (SNSF)¦¦CRSII5_180326pt_BR
dc.sponsorship.butantanThe State Secretariat for Education, Research and Innovation (SERI)¦¦ESKAS – 2017.0670pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.openairetypeArticle-
item.fulltextCom Texto completo-
item.grantfulltextembargo_29990101-
item.languageiso639-1English-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid0000-0002-6245-3166-
crisitem.author.orcid0000-0003-0890-9561-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journalissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journaleissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
Appears in Collections:Artigos de periódicos


Files in This Item:

Existing users please Login
10.1016j.bmc.2019.05.020.pdf
Size: 3.69 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show simple item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.