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It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates β-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some “hits” led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action. [ABSTRACT FROM AUTHOR]

Two new dimethylpyrano-isoflavones, named erymildbraedin A ( 4) and B ( 5), were isolated from the stem bark of the Cameroonian medicinal plant Erythrina mildbraedii, along with four known ones, the linear congeners, scandenone ( 1), erysenegalinsein M ( 2), 5,4′-dihydroxy-2′-methoxy-8-(3,3-dimethylallyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavone ( 3), and the angular isoflavone eryvarin B ( 6), and two other compounds, fraxidin and scoparone. Their structures were elucidated by the usual spectroscopic methods and isoflavone effects on the growth of human breast, prostate, and endometrial adenocarcinoma cells were determined. Isoflavones 1, 3, and 6 strongly inhibited the growth of all three cell lines, supporting the notion that a non-oxidized isoprenyl group at C-8 is requisite for cytotoxic activity. [ABSTRACT FROM AUTHOR]