The growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of seven phytocannabinoids and four terpenes were considered. On the side of ligand-based virtual screening, physico-chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug-like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure-based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (À9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted.Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.
The cytotoxicity of Ionic Liquids (ILs) has been raising attention in the context of the biological and environmental impact of their vast field of applications. It is ascertained that the...
A highly reactive and selective catalytic system comprising Cu(I) and a macrocyclic pyridine-containing ligand (PcÀ L) for the synthesis of 2-(penta-2,4-dien-1-ylidene) 3-oxoindolines from 4H-furo[3,2-b]indoles and diazoalkane is reported herein. The reaction sequence involves the initial formation of a coppercarbene by Cu(I)-catalyzed decomposition of a diazoalkane followed by copper-carbene to furoindole addition and successive furan ring-opening affording the final products. The reaction proved to be quite general, tolerating EWG as well as EDG substituents on the indole scaffold as well as acceptor or donor/acceptor carbene precursors and products were obtained in good to excellent yields. The proposed methodology allows to overcome some selectivity issues encountered performing similar transformations in the presence of gold(I)-carbenes. Interestingly, two of the 2-alkenylidene-3-oxoindolines are characterized by a second-order nonlinear optical response higher than that of Disperse Red One
Two sets of unprecedented push-pull isoquinolines, characterized by an opposite “dipolar moment” with respect to the longitudinal axis of the molecule, have been prepared. The key step of the approach...
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