Título:	Avaliação toxicológica aguda dos derivados diidropirimidinonas 4p E 4bc
Autor(es):	Matos, Larizza Hellen Santana
Orientador(es):	Mello, Maurício Homem de
Assunto:	Toxidade Câncer - farmacologia Citotoxicidade Histologia
Data de publicação:	24-Out-2017
Data de defesa:	2-Ago-2017
Referência:	MATOS, Larizza Hellen Santana. Avaliação toxicológica aguda dos derivados diidropirimidinonas 4p e 4bc. 2017. 133 f., il. Dissertação (Mestrado em Ciências Farmacêuticas)—Universidade de Brasília, Brasília, 2017.
Abstract:	Cancer is a complex and multifactorial disease that has a high incidence and mortality worldwide. Drugs used in conventional therapy have numerous adverse effects and resistance. The development safer and more effective antineoplastic agents. Monastrol emerged as an option for the treatment of cancer and dihydropyrimidinone derivatives were synthesized and its antitumor effect investigated. Compounds 4p and 4bc showed selective cytotoxicity for tumor cells in previous studies against adenocarcinoma (MCF-7 and MDA-MB-231) lines. In view of the in vitro results, the present study has as its objective the acute toxicological evaluation in vivo of these derivatives and to trace the bioavailability profile. Initially toxicity was assessed following oral administration of 4p and 4bc, and then further study by intravenous route only for 4bc, and no clinical signs of toxicity were observed at all doses and routes evaluated. Based on this study for oral exposure the compounds were classified as category 5 by the GHS. Further analysis showed no clinically relevant changes in feed intake, water intake, weight gain and organ index. Histological and anatomopathological studies revealed normality in all groups of the trials. Hematological and biochemical tests revealed abnormal parameters for oral administration (Leukocytes, Monocytes, Platelet Count, Urea) and intravenous (Leukocytes, Monocytes, Platelet Count, Urea and AST) were reported for all groups, indicating not to be an effect of exposure to DHPMs. The significant and clinically relevant difference reported between all treated groups and controls was revealed following intravenous administration of 4bc for the triglycerides and glucose parameters. No compounds were determined in the blood after acute oral and intravenous exposure through high performance liquid chromatography and luminescence assay. The results suggest low acute toxicity by the routes evaluated, and the continuity of the studies and toxicity is necessary and more deeply evaluate the pharmacokinetic profile of derivatives 4p and 4bc.
Unidade Acadêmica:	Faculdade de Ciências da Saúde (FS) Departamento de Farmácia (FS FAR)
Informações adicionais:	Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, 2017.
Programa de pós-graduação:	Programa de Pós-Graduação em Ciências Farmacêuticas
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DOI:	http://dx.doi.org/10.26512/2017.08.D.24865
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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