Detalhes bibliográficos
| Ano de defesa: |
2013 |
| Autor(a) principal: |
MORAES, Thiago Augusto Pereira de
 |
| Orientador(a): |
SILVA JUNIOR, Valdemiro Amaro da |
| Banca de defesa: |
JIMENEZ, George Chaves,
EVÊNCIO NETO, Joaquim |
| Tipo de documento: |
Tese
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Federal Rural de Pernambuco
|
| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Biociência Animal
|
| Departamento: |
Departamento de Morfologia e Fisiologia Animal
|
| País: |
Brasil
|
| Palavras-chave em Português: |
|
| Área do conhecimento CNPq: |
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| Link de acesso: |
http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/4606
|
Resumo: |
Cytotoxicity of 10 Amino-naphthoquinone (ANQ) was evaluated in cell lines MDA-MB-435 (melanoma), SF-295 (brain) and HCT-8 (colon), all human strains. Among the amino-naphthoquinones tested, five (2a, 9a, 6a, 5a and 7a) have cytotoxicity in cell lines tested. Among these, the sample was the seventh most active, showing IC50 values of 1.84 mg / mL for HCT-8, 1:33 / mL for MDA-MB-435 and 1.80 g / ml in strain SF-295. The same compound produced inhibition of cellular 99.51%, 100.11% and 99.50% for HCT-8, MDA-MB-435 and SF-295, respectively. In the following experiment aimed to determine the toxic effects and the safety threshold of synthetic amino-naphthoquinone ETHYL 2 - (1,4-dioxo-1,4-DIHYDRONAPHTHALEN-2-ylamino) ACETATE, administered in a single dose and different concentrations. For this purpose twenty-four mice (Mus musculus, Swiss albinos) males were divided according to dosage: Group I (treated with the 100μg/Kg aminoquinone (n = 6)), Group II (treated with 200μg/Kg of aminoquinona (n = 6)), Group III (300μg/Kg of aminoquinone treated (n = 6)), Group IV (treated with 600μg/Kg of aminoquinona (n = 6)). The animals were food fasted 6 hours and then treated intraperitoneally with the amino-naphthoquinone according to the prescribed dose. After administration of the doses experimental animals were evaluated for 180 minutes uninterrupted, and then every 24 hours in order to characterize the behavior of the animals through clinical signs for 72 hours. After toxicological evaluation of aminoquinona ETHYL 2 - (1,4-dioxo-1,4-DIHYDRONAPHTHALEN-2-ylamino) ACETATE through analysis of spontaneous activity was found depressing effect on the CNS in a dose-response relationship directly. The calculation of the LD50 test substance showed low levels of toxicity at doses less than 244.1125 ± 23.2883 mg.Kg-1. In subsequent experiments, eighteen mice with solid Ehrlich carcinoma were divided into control group (n = 6) and treated with methotrexate (n = 6; 71.7mg.kg-1) and treated with ethyl 2 - (1,4-dioxo-1,4-dihidronaphthalen-2-ylamino) acetate (n = 6; 20mg.kg-1). Four days after the cells of Ehrlich ascites tumor were implanted subcutaneously and the mice receiving methotrexate amino-naphthoquinone in a single dose. On the 8th day, methotrexate and amino-naphthoquinone 67% inhibited tumor growth by 58% and 67%, respectively compared to the control group. No substantial change in the biochemical and histopathologic findings were observed in the liver and kidneys of animals treated with amino-naphthoquinone. The amino-naphthoquinone ethyl 2 - (1,4-dioxo-1 ,4-dihidronaphthalen-2-ylamino) acetate can be considered a promising drug in cancer therapy. However, future studies should be performed to determine the mechanism of action of this substance. |
