Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus Aspergillus fischeri MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.

An unreported prenylated indole derivative hydroxytakakiamide (4) was isolated, together with the previously described ergosterol (1), ergosterol acetate (2), and (3R)-3-(1H-indol-3-ylmethyl)-3, 4-dihydro-1H-1,4-benzodiazepine-2,5-dione (3), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in 3 was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and 2 were evaluated, together with acetylaszonalenin (5) and helvolic acid (6), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while 2, 5, and 6 displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor 2, 5, and 6 affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of 2, 5, and 6 were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that 6 has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while 2 did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than 6 on the three antinociceptive targets. On the other hand, 5 has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.

A new approach to microbial production of gallic acid / Uma nova abordagem para produção microbiana de ácido gálico

In a new approach to microbial gallic acid production by Aspergillus fischeri MTCC 150, 40gL-1 oftannic acid was added in two installments during the bioconversion phase of the process (25gL-1 and 15gL-1 at 32 and 44h respectively). The optimum parameters for the bioconversion phase were found to be temperature: 35ºC, pH: slightly acidic (3.3-3.5), aeration: nil and agitation: 250 rpm. A maximum of 71.4 percent conversion was obtained after 71h fermentation with 83.3 percent product recovery. The yield was 7.35 g of gallic acid per g of biomass accumulated and the fermenter productivity was 0.56 g of gallic acid produced per liter of medium per hour.

Em uma nova abordagem para produção de ácido gálico por Aspergillus fischeri MTCC 150, adiciona-se 40 g.L-1 de ácido tânico em dois momentos da fase de bioconversão do processo (25 g.L-1 e 15 g.L-1 a 32h e 44h, respectivamente). Os parâmetros ótimos para a fase de bioconversão foram: temperatura 35ºC, pH levemente ácido (3,3 a 3,5), nenhuma aeração e agitação 250 rpm. Um máximo de 71,4 por cento de conversão foi obtido após 71h de fermentação, com 83,3 por cento de recuperação do produto. O rendimento foi 7,35g de ácido gálico por g de biomassa acumulada e a produtividade do fermentador foi 0,56g de ácido gálico por litro de meio por hora.