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Anti-carie and antiproliferative effect of 7-epiclusianone, isolated from Rheedia genus plant / Avaliação das atividades anticarie e antiproliferativa da 7-epiclusianona isolada da planta do genero Rheedia
Ramiro Mendonça Murata
DATA DE PUBLICAÇÃO
Considering the great use of plants as medicinal substances in the popular medicine, it is critical to investigate their biological and chemical properties in order to not only help to enhance our understanding of the therapeutic potential of these natural products, but also how to make them more effective pharmacological agents. The enormous biodiversitiy of Brazil flora appears as an important source of new pharmacological agents. In this way, Rheedia genus showed the presence of flavonoids, xanthones and polyprenylated benzophenones with proved actions against important pathogens Overall, aim of this study was to evaluate the antimicrobial and atitumoral effect of the 7 -epiclusianone, isolated compound of the Rheedia genus planto Therefore, four studies were carried out. In study 1, the influence of 7-epiclusianone was evaluated on glucans production by purified glucosyltransferases (GTFs), on membrane-associated F-ATPase, on glycolytic activities and insoluble glucans composition/acidogenicity of S. mutans biofilmes. In study 2, the influence of 7-epiclusianone, alone or in combination with fluoride, on S. mutans biofilms and caries development in vivo was evaluated. In study 3, the ant microbial activity of the 7-epiclusianone was assessed by determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) against S. mutans. In study 4, the influence of 7 -epiclusianone in a differential antiproliferative activity against a human cancer celllines. In study 1, the synthesis of glucans by glucosyltransferases B and C was remarkably reduced by 7-epiclusianone showing more than 80% inhibition of enzymatic activityat a concentration of 100 ~g/m1. The glycolytic pH-drop by S. mutans cells was also disrupted by 7-epiclusianone; an effect that can be attributed, in part, to inhibition of F-ATPase activity (61.1:t3.0 % inhibition at 100/lg/mL). The extracelIular insoluble polysaccharide concentration and acidogenicity of the biofilms were significant1y reduced by the test agent (P<0.05). In study 2, biofilms treated with 7-epiclusianone, alone or in combination with F, displayed less biomass and insoluble glucans than the positive control (tluoride) (p<0.05). The biological effect of 7-epiclusianone was great1y enhanced when used in combination with F. Furthermore, the combination of 7-epiclusianone with F was highlyeffective in preventing caries development in rats. In study 3, 7-epiclusian one was effective in inhibiting the growth of S. mutans (MIC 2.5-5 Ilg/ml and MBCIO-20 Ilg/ml). In study 4, 7 -epiclusianone displayed significant cytotoxic activity for alI celIlines. The ICso, half maximal inhibitory concentration, of 7-epiclusianone was significantly more potent positive control (doxorubicin) against melanoma (UACC-62), breast-resitant (NCI-ADR), ovarian (OVCAR), and lung (NCI-460) celIs. In conclusion, 7-epiclusianone have relevant antimicrobial and atiproliferative activity and are promising anti-caries and antitumoral agents.
produtos com ação antimicrobiana produtos biologicos caries dentarias ensaios de seleção de medicamentos antitumorais biological products drug screening assays products with antimicrobial action dental caries