Pesquisa de atividade antitumoral e mutagênica in vitro de produtos naturais
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Data
2008-04-14
Autores
Gomes, Juliana Pizarro Martins [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O presente trabalho avaliou a citotoxicidade in vitro de produtos naturais (terpenos, iridóides e derivados fenólicos) em linhagens celulares de adenocarcinoma murino de mama (LM3) e de pulmão (LP07), buscando uma possível correlação entre estrutura molecular e atividade antitumoral. A ordem de citotoxicidade na linhagem LM3 foi tingenona> pristimerina> plumericina> cromeno> paclitaxel> escandenina> acetato de bauerenila> ácido p-cumárico> ácido clorogênico. Na linhagem LP07, a exceção é a inversão de posição entre os ácidos clorogênico e p-cumárico e escandenina e paclitaxel. Pristimerina, tingenona, plumericina e o cromeno foram mais ativos que o controle positivo, taxol. Os nor-triterpenos pentacíclicos quinonametídeos tingenona (IC50=0,002 μmol/mL em LP07 e 0,003 μmol/mL em LM3) e pristimerina (IC50=0,005 μmol/mL em LP07 e LM3) apresentaram a maior citotoxicidade nas linhagens tumorais. A avaliação da relação estrutura e atividade indicaram os anéis A e B essenciais para o efeito citotóxico, devido à cetona ,ß-insaturada. A interação de pristimerina e tingenona com N-acetilcisteína foi confirmada por métodos espectrofotométricos e biológicos, constituindo um provável mecanismo de ação das substâncias. A atividade mutagênica das moléculas mais promissoras, pristimerina, tingenona e plumericina foi avaliada in vitro na presença e ausência de ativação metabólica (S9) e não demonstraram mutagenicidade (RM<2).
This study evaluates the in vitro cytotoxicity of natural products such as terpenes, iridoids, and phenolic derivatives in the cell lines of adenocarcinoma murine of the breast (LM3) and lung (LP07). The study attempted to identify possible correlations between the molecular structure of these natural products and anticancer activity. The sequence for cytotoxic activity in the LM3 line was tingenone> pristimerin> plumericine> cromene> paclitaxel> scandenin> bauerenyl acetate> p-coumaric acid> chlorogenic acid. This sequence was similar to the LP07 cell line, however the exception was the inverse order between clorogenic and p-coumaric acid and between scandenine and taxol. Pristimerine, tingenone, plumericine and cromene were more potent than taxol, the positive control substance in this study in all cell lines. The quinone-methide triterpene tingenone (IC50=0,002 μmol/mL in LP07 and 0,003 μmol/mL in LM3) and pristimerin (IC50=0,005 μmol/mL in LP07 and LM3) showed the largest level of cytotoxicity in the cell lines. The structure-activity relationship suggests that rings A and B containing an , ßunsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between pristimerin and tingenone with N-acetilcysteine was proved by byological and spectrophotometric methods, estabilishing a likely action mechanism to these compounds. The in vitro mutagenic activity was evaluated for the most promising compounds: pristimerine, tingenone and plumericine, and they did not show mutagenic potential (RM<2).
This study evaluates the in vitro cytotoxicity of natural products such as terpenes, iridoids, and phenolic derivatives in the cell lines of adenocarcinoma murine of the breast (LM3) and lung (LP07). The study attempted to identify possible correlations between the molecular structure of these natural products and anticancer activity. The sequence for cytotoxic activity in the LM3 line was tingenone> pristimerin> plumericine> cromene> paclitaxel> scandenin> bauerenyl acetate> p-coumaric acid> chlorogenic acid. This sequence was similar to the LP07 cell line, however the exception was the inverse order between clorogenic and p-coumaric acid and between scandenine and taxol. Pristimerine, tingenone, plumericine and cromene were more potent than taxol, the positive control substance in this study in all cell lines. The quinone-methide triterpene tingenone (IC50=0,002 μmol/mL in LP07 and 0,003 μmol/mL in LM3) and pristimerin (IC50=0,005 μmol/mL in LP07 and LM3) showed the largest level of cytotoxicity in the cell lines. The structure-activity relationship suggests that rings A and B containing an , ßunsaturated carbonyl group are essential for the observed cytotoxic activity. The interaction between pristimerin and tingenone with N-acetilcysteine was proved by byological and spectrophotometric methods, estabilishing a likely action mechanism to these compounds. The in vitro mutagenic activity was evaluated for the most promising compounds: pristimerine, tingenone and plumericine, and they did not show mutagenic potential (RM<2).
Descrição
Palavras-chave
Produtos naturais (Química), Mutagenicidade, Antitumorais, Química farmacêutica, Produtos Naturais - Citotoxicidade, Natural products - Cytotoxicity
Como citar
GOMES, Juliana Pizarro Martins. Pesquisa de atividade antitumoral e mutagênica in vitro de produtos naturais. 2008. 71 f. Dissertação (mestrado) - Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, 2008.