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Master's Dissertation
DOI
10.11606/D.42.2012.tde-23042013-122652
Document
Author
Full name
Márcia Ferreira da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Katzin, Alejandro Miguel (President)
Fogaça, Andréa Cristina
Toledo, Erika Suzuki de
Title in Portuguese
Estudos in vitro de potenciais antimaláricos nos estágios intraeritrocítico de Plasmodium falciparum.
Keywords in Portuguese
Plasmodium
Antimaláricos
Enzimas
Malária
Sinergismo de drogas
Abstract in Portuguese
Nesta dissertação, identificou-se que as drogas esqualestatina, fosmidomicina, risedronato e nerolidol apresentam atividades sinérgicas e aditivas quando administradas em cultura de P. falciparum. Esses resultados contribuem para a compreensão da biologia do parasita e abrem estudos para possíveis antimaláricos. Identificou-se a especificidade da droga esqualestatina inibidora da enzima fitoeno sintase por meio de marcações metabólicas utilizando precursor radioativo ([3H]GGPP), e análise pela técnica de cromatografia (RP-HPLC). Realizou-se testes de inibição para determinar o valor da IC50 na linhagem pRM2-Fito-HA, a qual encontra-se super expressando enzima fitoeno sintase e encontrou-se um valor IC50 de 5 mM para o isolado 3D7 enquanto que para a linhagem pRM2-Fito-HA foi de 30 mM. Demonstrando assim que a enzima fitoeno sintase é o principal, senão único alvo da esqualestatina em P. falciparum, o que sugere que este composto ou derivado do mesmo são potenciais antimalaricos.
Title in English
In vitro studies of potential antimalarial intraeritrocítico stages of Plasmodium falciparum
Keywords in English
Plasmodium
Antimalarials
Enzymes
Malaria
Synergism of drugs
Abstract in English
In this thesis, we found that the drug squalestatin, fosmidomicina, risedronate, nerolidol have synergistic and additive activity when administered in cultured P. falciparum. These results contribute to the understanding of the biology of the parasite and open studies for potential antimalarials. We identified the specific drug squalestatin inhibiting phytoene synthase enzyme by using metabolic markers radioactive precursor ([3H] GGPP) by the technique of analysis and chromatography (RP-HPLC). Held inhibition tests to determine the IC50 value of the strain in pRM2-Phyto-HA, which is super expressing phytoene synthase enzyme and met an IC50 value of 5 microM to isolate 3D7 whereas for strain pRM2 -Phyto-HA was 30 mM. Thus demonstrating that the enzyme phytoene synthase is the primary, if not sole target of squalestatin in P. falciparum, which suggests that this compound or derivative thereof as potential antimalarials.
 
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Publishing Date
2013-06-04
 
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