Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition

Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. One of its main consequences is memory loss, which is related to downstream effectors of cyclic adenosine monophosphate (cAMP). A well-established strategy to avoid cAMP degradation is the inhibition of phosphodiesterase (PDE). In recent years, GEBR-32a has been shown to possess selective inhibitory properties against PDE type 4 family members, resulting in an improvement in spatial memory processes without the typical side effects that are usually correlated with this mechanism of action. In this work, we performed the HPLC chiral resolution and absolute configuration assignment of GEBR-32a. We developed an efficient analytical and semipreparative chromatographic method exploiting an amylose-based stationary phase, we studied the chiroptical properties of both enantiomers and we assigned their absolute configuration by 1H-NMR (nuclear magnetic resonance). Lastly, we measured the IC50 values of both enantiomers against both the PDE4D catalytic domain and the long PDE4D3 isoform. Results strongly support the notion that GEBR-32a inhibits the PDE4D enzyme by interacting with both the catalytic pocket and the regulatory domains

Anti-multiple myeloma potential of secondary metabolites from Hibiscus sabdariffa

Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse eects, including neurotoxicity. As a part of our ongoing efforts to discover new potential therapies against MM, we prepared Hibiscus sabdariffa extracts obtained by a microwave-assisted solvent extraction and investigate their activity by in vitro assays on the RPMI-8226 cell line. The bioguided fractionation of the crude ethanolic extract allowed the identification of HsFC as the most effective extract. We assessed cell viability (MTT and Tripan blue test), cell migration (Boyden chamber assay), and neurotoxicity (DRG neurotoxicity assay). The promising results prompted us to further fractionate HsFC and we obtained two molecules effective against RPMI-8226 cells without neurotoxic effects at their active concentrations. Moreover, both compounds are able to significantly reduce cell migration

The Request Testability Methodology for VHDL Based ASIC Design

The Request Testability Methodology for VHDL Based ASIC Desig

Implicit Testability Techniques for VHDL Based ASIC Design

Implicit Testability Techniques for VHDL Based ASIC Desig

An Extended Testing Methodology for VHDL Based High-Level Design

An Extended Testing Methodology for VHDL Based High-Level Desig

New insight into pectin effects on mesophyll conductance in four species of deciduous Forest

The amount of pectin in the cell wall is considered a critical element regulating cell wall porosity. Thus, it is likely to influence the diffusional processes particularly that from the substomatal cavities to the carboxylation sites in the chloroplast stroma (i.e. mesophyll conductance, gm). We analyzed in four deciduous species (Acer campestre, Crateaugus monogyna, Corylus avellana, Quercus robur) the correlation between pectin and g m in two phase of leaves development (i.e. mature green leaves and senescent leaves). Results showed that in A. campestre, C. monogyna and Q. robur to higher value of pectin in mature green leaves corresponded the higher g m value. Taking into account this result, we can assume that a higher amount of pectins is associated to an increased cell wall hydrophilicity and elasticity, thus increasing gm because CO2 molecules cross the wall dissolved in water. An opposite behavior was observed in C. avellana