Banca de QUALIFICAÇÃO: VALESKA SANTANA DE SENA PEREIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE: VALESKA SANTANA DE SENA PEREIRA
DATA: 20/08/2015
HORA: 14:00
LOCAL: Sala Carl Peter von Dietrich - Depto. de Bioquímica - CB/UFRN
TÍTULO:

In vitro antiplasmodial activity, toxicity and investigate the mechanism of action in the isoprenoid pathway of 2- anilino-3-hydroxy-1,4-naphthoquinone derivatives

PALAVRAS-CHAVES:

Plasmodium falciparum, antimalarial drugs, naphthoquinones, cytotoxicity, isoprenoid pathway.

PÁGINAS: 22
GRANDE ÁREA: Ciências Biológicas
ÁREA: Parasitologia
SUBÁREA: Protozoologia de Parasitos
RESUMO:

Plasmodium falciparum has shown multidrug resistance, leading to the need for the development of new drugs with novel targets, as the synthesis of isoprenic precursors, excellent targets because they are different in the human host. Naphthoquinone derivatives has been described as potentially promising for the development of anti-malarial leader molecules. Our aim was to evaluate the in vitro antiplasmodial activity, cytotoxicity and investigate one possible action mechanism of two derivatives of naphthoquinones. The naphthoquinones derivatives analyzed had antiplasmodial activity against asexual blood stages of Plasmodium falciparum, strains 3D7 and Dd2. The cell viability in vitro against RAW Cell Line displayed IC50 = 483.5 and 714.9 μM, whereas in primary culture tests using murine macrophages, IC50 were 315.8 and 532.6 μM for naphthoquinones derivatives 4a and 4c respectively, besides no caused hemolysis at the doses tested. The in vivo acute toxicity assays exhibited a significant safety margin indicated by a lack of systemic ans behavioral toxicity up to 300 mg/kg. We also suggest that this drug seems to inhibit the synthesis of isoprenic precursors, particularly the menaquinone and tocopherol. Thereby, these derivatives have a high potential for the development of news antimalarial drugs since they showed low toxicity and antiplasmodial activity satisfactory.

MEMBROS DA BANCA:
Interno - 1880243 - DANIEL CARLOS FERREIRA LANZA
Presidente - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Externo ao Programa - 1752367 - PAULO MARCOS DA MATTA GUEDES