Obtenção de derivados do Resveratrol por biotransformações e avaliação das atividades biológicas

Abstract

Resumo

Resumo: Considerando-se que dificilmente uma substancia organica resiste a acao catalitica dos diversos sistemas enzimaticos presentes em organismos vivos, alteracoes na estrutura quimica de moleculas organicas podem ser realizadas atraves de sistemas envolvendo microrganismos e as alteracoes promovidas podem resultar em mudancas consideraveis em sua acao farmacologica. O resveratrol e uma substancia fenolica conhecido por varias atividades farmacologicas, das quais se destacam as antioxidantes e anticancerigenas. Em contraste, possui baixa biodisponibilidade in vivo. Visando maior atividade biologica, mudancas na estrutura quimica do transresveratrol envolvendo biotransformacao com dezenove especies de fungos foram realizadas. Desses, somente o Bipolaris sorokiniana e o Penicillium sp. (64) levaram a resultados positivos em sua biotransformacao. Neste contexto, a biotransformacao do trans-resveratrol pelo B. sorokiniana resultou na sua dimerizacao, levando ao transdehidrodimero do resveratrol, enquanto a reacao com Penicillium sp. (64) levou a formacao de trans-resveratrol-4'-O-metil-5-O-acetil-3-O-?-glucosideo, substancia pela primeira vez descrita. Ao se avaliar o efeito dessas substancias sobre o comportamento de celulas das linhagens McCoy, B16F10 e Hela com o ensaio do MTT, observou-se que o trans-resveratrol-4'-O-metil-5-O-acetil-3-O-?-glucosideo inibiu a proliferacao com perfil semelhante, porem significativamente maior, que o seu precursor, em contraste com o trans-dehidrodimero do resveratrol, o qual promoveu significativo aumento do numero de celulas. Interessante ressaltar que ambos os efeitos, tanto de inibicao quanto de inducao da proliferacao, foram dependentes da dose. Estudos mais aprofundados sao necessarios para definicao do real potencial biologico desses produtos.

Abstract: Considering that an organic compound hardly ever resists the catalystic action of the several enzymatic systems present in living organisms, changes in chemical structure of organic molecules can be accomplished through systems involving microorganisms. The structural changes in the ending products may result in considerable enhancement of their pharmacological potential. Contrasting with its low bioavailability in vivo, resveratrol is a phenolic compound widely known by its different pharmacological activities, especially as an antioxidant and anticancer agent. With the aim of achieving higher biological activity, changes in the chemical structure of the trans-resveratrol involving biocatalysis with nineteen species of fungi have been performed. Of these, only Bipolaris sorokiniana and Penicillium sp. (64) led to positive results in which the biotransformation of trans-resveratrol by B. sorokiniana resulted in its dimerization, leading to the formation of trans-resveratrol dehydrodimer, while the reaction with Penicillium sp. (64) resulted in the formation of trans-resveratrol-4'-Omethyl- 5-O-acetyl-3-O-?-glucoside, a compound never reported. To evaluate whether these compounds were biologically active, their influence on the behavior of McCoy, B16F10, and Hela cell lines were studied using the MTT assay. The results showed that the trans-resveratrol-4'-O-methyl-5-O-acetyl-3-O-?-glucoside derivative inhibited the proliferation of all cell lines tested with similar profile, but significantly higher, than its precursor. In contrast, the trans-dehydrodymer led to a significant increase in the number of cells. Worthy of note is the fact that, although having opposite effects, both were dose-dependent. Further studies are required for defining the real biological potential of these products.