Síntese e avaliação das atividades fitotóxica e antiproliferativa de isobenzofuran-1(3H)-onas C-3 funcionalizadas

• Autor(a) principal: Pereira, Wagner Luiz
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: LOCUS Repositório Institucional da UFV
• Texto Completo: http://locus.ufv.br/handle/123456789/2145
• topic: Isobenzofuran-1(3H)-onas; Fitalidas; Atividade antiproliferativa; Sobenzofuran-1(3H)-ones; Phtalides; Antiproliferative activity; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA

The present investigation aimed to synthesize a series of isobenzofuran-1(3H)-ones (phtalides) structurally similar to the secondary metabolite cryphonectric acid. The substances were prepared via condensation, aromatization and acetylation reactions. The identity of the synthesized compounds were confirmed based on IR, 1H and 13C NMR (1D), HMBC and HSQC 2D experiments and MS analyses. The structure of 3-(2- hydroxy-4,4- imethyl-6-oxo-cyclohexen-1-yl)isobenzofuran-1(3H)-one was also investigated by X-ray analysis. The isobenzofuran-1(3H)-ones was evaluated in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. Among the twelve evaluated compounds, four were completely inactive in interfering with photosynthetic electron. Other four phtalides were found to inhibit the basal rate. In this case, the most active derivative 2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-1Hindene- 1,3(2H)-dione inhibited the basal electron transport by 56%. The other derivatives acted as uncouplers. The phtalides were also evaluated in vivo as the ability to interfere with the radical growth of cucumber (Cucumis sativus) and sorghum (Sorghum bicolor). 3-(2,6- ihydroxy-4- isopropylphenyl)-isobenzofuran-1(3H)-one caused more than 70% inhibition of Sorghum bicolor shoot elongation. This effect was comparable to the 75% inhibition caused by commercial herbicide glyphosate on the same species. Considering the existence of examples described in the literature isobenzofuran-1(3H)-ones C-3 functionalized showing cytotoxic effects against different tumor cell lines, the antiproliferative activity of the twelve isobenzofuranones were evaluated against the cell lines U937 (lymphoma) and K562 (myeloid leukemia). Two isobenzofuranones were more effective in inhibitting proliferation of K562 cells and presented IC50 lower than etoposide (VP-16) used as positve control in the experiments. The in silico favorable drug-like parameters predicted suggest that the isobenzofuranones prepared in this work possess good physicochemical properties that qualify them as promising candidates for future studies.