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A series of 4-azapodophyllotoxin derivatives with modified rings B and E have been synthesized using allylpolyalkoxybenzenes from parsley seed oil. The targeted molecules were evaluated in vivo in a phenotypic sea urchin embryo assay for antimitotic and tubulin destabilizing activity. The most active compounds identified by the in vivo sea urchin embryo assay featured myristicin-derived ring E. These molecules were determined to be more potent than podophyllotoxin. Cytotoxic effects of selected molecules were further confirmed and evaluated by conventional assays with A549 and Jurkat human leukemic T-cell lines including cell growth inhibition, cell cycle arrest, cellular microtubule disruption, and induction of apoptosis. The ring B modification yielded 6-OMe substituted molecule as the most active compound. Finally, in Jurkat cells, compound induced caspase-dependent apoptosis mediated by the apical caspases-2 and -9 and not caspase-8, implying the involvement of the intrinsic caspase-9-dependent apoptotic pathway.

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In this study we compared the effects of transcranial direct current stimulation (tDCS) in the subacute and chronic stages of post-stroke recovery. Anodal/sham tDCS was applied to the primary motor cortex of stroke patients in these stages of recovery in a cross-over design. The Jebsen-Taylor hand function test was employed. The repeated-measure ANOVA showed significant influence of the stimulation type and test performance time (during/after tDCS) with no overall influence of recovery stage. The interaction TYPE Ã TIME Ã STAGE was significant. The effect after anodal tDCS in the subacute stage was significantly higher compared to the effects in all relevant conditions including the chronic stage. Therefore, tDCS treatment in the subacute stage of recovery can be superior, at least for some patients, to treatment in the chronic stage.