Show simple item record

dc.contributor.advisorGnoatto, Simone Cristina Baggiopt_BR
dc.contributor.authorWaechter, Fernandapt_BR
dc.date.accessioned2017-05-17T02:36:28Zpt_BR
dc.date.issued2014pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/158088pt_BR
dc.description.abstractChronic 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.en
dc.format.mimetypeapplication/pdf
dc.language.isoengpt_BR
dc.rightsOpen Accessen
dc.subjectBetulinic aciden
dc.subjectFarmáciapt_BR
dc.subjectAntitumoren
dc.subjectTriptolideen
dc.subjectChonic myeloid leukemiaen
dc.subjectFluorinationen
dc.titleDesign, synthesis, and biological evaluation of betulinic acid derivatives as new antitumor agentspt_BR
dc.typeTrabalho de conclusão de graduaçãopt_BR
dc.contributor.advisor-coSilva, Gloria Narjara Santos dapt_BR
dc.identifier.nrb001019073pt_BR
dc.degree.grantorUniversidade Federal do Rio Grande do Sulpt_BR
dc.degree.departmentFaculdade de Farmáciapt_BR
dc.degree.localPorto Alegre, BR-RSpt_BR
dc.degree.date2014pt_BR
dc.degree.graduationFarmáciapt_BR
dc.degree.levelgraduaçãopt_BR


Files in this item

Thumbnail
   

This item is licensed under a Creative Commons License

Show simple item record