Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Tipo de documento: | Trabalho de conclusão de curso |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/158088 |
Resumo: | Chronic myeloid leukemia (CML) is a cancer that is currently treated with imatinib, however, resistance to this drug usually develops over time. Triterpenes such as betulinic acid can be analogues of triptolide, a compound recently shown to be active against CML cells resistant to imatinib. The aim of this study was to perform modifications on betulinic acid based on the structure-activity relationship of triptolide to generate new analogues, and evaluate their cytotoxicity. The main modification performed was fluorination on C-28. A total of 5 analogues were synthesized, being 3 previously described and 2 novel compounds. The MTT assay was performed using HeLa, B16F10 and HaCaT cell lines. The results show that the presence of fluorine in the molecule has an important role in increasing the antitumor activity. However, fluorination also enhanced the cytotoxicity on non-tumor cells, being betulinic acid less toxic than its tested derivatives. Considering B16F10 cells, compound 3 was the most active and selective, with IC50 of 1.9 μM, being considered a promising agent for the treatment of melanoma. Further studies are needed to investigate the antitumor activity in CML cells, since the mechanism of death and activity may be different for different cell lines. |
id |
UFRGS-2_002721efa0b8ff050991e61ed9ca956d |
---|---|
oai_identifier_str |
oai:www.lume.ufrgs.br:10183/158088 |
network_acronym_str |
UFRGS-2 |
network_name_str |
Repositório Institucional da UFRGS |
repository_id_str |
|
spelling |
Waechter, FernandaGnoatto, Simone Cristina BaggioSilva, Gloria Narjara Santos da2017-05-17T02:36:28Z2014http://hdl.handle.net/10183/158088001019073Chronic myeloid leukemia (CML) is a cancer that is currently treated with imatinib, however, resistance to this drug usually develops over time. Triterpenes such as betulinic acid can be analogues of triptolide, a compound recently shown to be active against CML cells resistant to imatinib. The aim of this study was to perform modifications on betulinic acid based on the structure-activity relationship of triptolide to generate new analogues, and evaluate their cytotoxicity. The main modification performed was fluorination on C-28. A total of 5 analogues were synthesized, being 3 previously described and 2 novel compounds. The MTT assay was performed using HeLa, B16F10 and HaCaT cell lines. The results show that the presence of fluorine in the molecule has an important role in increasing the antitumor activity. However, fluorination also enhanced the cytotoxicity on non-tumor cells, being betulinic acid less toxic than its tested derivatives. Considering B16F10 cells, compound 3 was the most active and selective, with IC50 of 1.9 μM, being considered a promising agent for the treatment of melanoma. Further studies are needed to investigate the antitumor activity in CML cells, since the mechanism of death and activity may be different for different cell lines.application/pdfengFarmáciaBetulinic acidAntitumorTriptolideChonic myeloid leukemiaFluorinationDesign, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agentsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisUniversidade Federal do Rio Grande do SulFaculdade de FarmáciaPorto Alegre, BR-RS2014Farmáciagraduaçãoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001019073.pdf001019073.pdfTexto completo (inglês)application/pdf545995http://www.lume.ufrgs.br/bitstream/10183/158088/1/001019073.pdf47154010bf4e47b866e6d1612a169b0aMD51TEXT001019073.pdf.txt001019073.pdf.txtExtracted Texttext/plain28157http://www.lume.ufrgs.br/bitstream/10183/158088/2/001019073.pdf.txtf9632584c843a28cfb40c4d70532be19MD52THUMBNAIL001019073.pdf.jpg001019073.pdf.jpgGenerated Thumbnailimage/jpeg1136http://www.lume.ufrgs.br/bitstream/10183/158088/3/001019073.pdf.jpg6842c06a4dddd1cf01212e2be604521dMD5310183/1580882022-06-12 04:41:28.807141oai:www.lume.ufrgs.br:10183/158088Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-06-12T07:41:28Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
title |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
spellingShingle |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents Waechter, Fernanda Farmácia Betulinic acid Antitumor Triptolide Chonic myeloid leukemia Fluorination |
title_short |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
title_full |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
title_fullStr |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
title_full_unstemmed |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
title_sort |
Design, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agents |
author |
Waechter, Fernanda |
author_facet |
Waechter, Fernanda |
author_role |
author |
dc.contributor.author.fl_str_mv |
Waechter, Fernanda |
dc.contributor.advisor1.fl_str_mv |
Gnoatto, Simone Cristina Baggio |
dc.contributor.advisor-co1.fl_str_mv |
Silva, Gloria Narjara Santos da |
contributor_str_mv |
Gnoatto, Simone Cristina Baggio Silva, Gloria Narjara Santos da |
dc.subject.por.fl_str_mv |
Farmácia |
topic |
Farmácia Betulinic acid Antitumor Triptolide Chonic myeloid leukemia Fluorination |
dc.subject.eng.fl_str_mv |
Betulinic acid Antitumor Triptolide Chonic myeloid leukemia Fluorination |
description |
Chronic myeloid leukemia (CML) is a cancer that is currently treated with imatinib, however, resistance to this drug usually develops over time. Triterpenes such as betulinic acid can be analogues of triptolide, a compound recently shown to be active against CML cells resistant to imatinib. The aim of this study was to perform modifications on betulinic acid based on the structure-activity relationship of triptolide to generate new analogues, and evaluate their cytotoxicity. The main modification performed was fluorination on C-28. A total of 5 analogues were synthesized, being 3 previously described and 2 novel compounds. The MTT assay was performed using HeLa, B16F10 and HaCaT cell lines. The results show that the presence of fluorine in the molecule has an important role in increasing the antitumor activity. However, fluorination also enhanced the cytotoxicity on non-tumor cells, being betulinic acid less toxic than its tested derivatives. Considering B16F10 cells, compound 3 was the most active and selective, with IC50 of 1.9 μM, being considered a promising agent for the treatment of melanoma. Further studies are needed to investigate the antitumor activity in CML cells, since the mechanism of death and activity may be different for different cell lines. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014 |
dc.date.accessioned.fl_str_mv |
2017-05-17T02:36:28Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/bachelorThesis |
format |
bachelorThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/158088 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001019073 |
url |
http://hdl.handle.net/10183/158088 |
identifier_str_mv |
001019073 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRGS instname:Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
instname_str |
Universidade Federal do Rio Grande do Sul (UFRGS) |
instacron_str |
UFRGS |
institution |
UFRGS |
reponame_str |
Repositório Institucional da UFRGS |
collection |
Repositório Institucional da UFRGS |
bitstream.url.fl_str_mv |
http://www.lume.ufrgs.br/bitstream/10183/158088/1/001019073.pdf http://www.lume.ufrgs.br/bitstream/10183/158088/2/001019073.pdf.txt http://www.lume.ufrgs.br/bitstream/10183/158088/3/001019073.pdf.jpg |
bitstream.checksum.fl_str_mv |
47154010bf4e47b866e6d1612a169b0a f9632584c843a28cfb40c4d70532be19 6842c06a4dddd1cf01212e2be604521d |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS) |
repository.mail.fl_str_mv |
|
_version_ |
1801224531247890432 |