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A series of thirty-three alkynyl and β-ketophosphonates were evaluated for their in vitro acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitory activities using Ellman’s spectrophotometric method. None of the examined compounds inhibited AChE activity at tested concentrations while twenty-nine of them showed significant and selective inhibition of BChE with IC 50 values between 38.60 µM and 0.04 µM. In addition, structure-activity relationships were discussed. The most effective inhibitors were the dibutyl o -methoxyphenyl alkynylphosphonate 3dc and dibutyl o -methoxyphenyl β-ketophosphonate 4dc . Activities of most potent compounds were also compared with a commercial organophosphorus compound. These results could inspire the design of new inhibitors with stronger activity against BChE. [ABSTRACT FROM AUTHOR]

Wild cardoon (Cynara cardunculus L. var. sylvestris Lam.) exhibits a particular adaptability to the Mediterranean environment. Aiming to introduce its cultivation in the degraded areas of Sicily, it seemed interesting to study seed germination in the typical stress conditions of this environment.Our results showed a good variability in salinity and water stress resistance among the populations. Moreover six of them exhibited higher germination percentages in polyethylene glycol than in NaCl.Therefore wild cardoon may be utilized as genetic material to select lines suitable to the cultivation in semi-arid conditions of Mediterranean environment. [Copyright &y& Elsevier]

[Display omitted] • Synthesis of cholinesterase inhibitors, fusing tacrine and the alkaloid solanocapsine. • Inhibition against AChE and BuChE enzymes at nM range was achieved. • Improved inhibition of BuChE was achieved since it could better allocate big compounds. • Docking and molecular dynamic studies suggest that they could act as dual inhibitors. To date, Alzheimer's disease is the most alarming neurodegenerative disorder worldwide. This illness is multifactorial in nature and cholinesterase inhibitors have been the ones used in clinical treatments. In this context, many of these drugs selectively inhibit the acetylcholinesterase enzyme interacting in both the active site and the peripheric anionic site. Besides, some agents have exhibited extensive benefits being able to co-inhibit butyrylcholinesterase. In this contribution, a strategy previously explored by numerous authors is reported; the synthesis of hybrid cholinesterase inhibitors. This strategy uses a molecule of recognized high inhibitory activity (tacrine) together with a steroidal alkaloid of natural origin using different connectors. The biological assays demonstrated the improvement in the inhibitory activity compared to the alkaloidal precursor, together with the reinforcement of the interactions in multiple sites of the enzymatic cavity. This strategy should be explored and exploited in this area. Docking and molecular dynamic studies were performed to explain enzyme-ligand interactions, assisting a structure–activity relationship analysis. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of new α-aminophosphonate-tetrahydroisoquinoline hybrids were synthetized by a simple and economical approach. • Most compounds displayed potent and selective activity against BChE. • Compound 3bc resulted to be the most active reversible and non-competitive inhibitor of BChE with an IC 50 value of 9 nM. • Molecular modelling and ADME predictions suggested the potential of hybrids as leads in the treatment of Alzheimer's disease. A series of 19 novel α-aminophosphonate-tetrahydroisoquinoline hybrids were synthesized through a cross dehydrogenative coupling reaction between N -aryl-tetrahydroisoquinolines and dialkylphosphites, using tert -butyl hydroperoxide as oxidazing agent. This simple procedure provided products with high atom economy and moderate to high yields. In vitro cholinesterase inhibitory activity of these compounds was evaluated. All the synthesized compounds showed good to excellent selective inhibition against butyrylcholinesterase. Compound 3bc was found to be the most active derivative with an IC 50 of 9 nM. Molecular modelling studies suggested that the inhibitor is located in the peripheral anionic site (PAS) of the enzyme and interacts with some residue of the catalytic anionic site. Kinetic studies revealed that 3bc acts as a non-competitive inhibitor. Predicted ADME showed good pharmacokinetics and drug-likeness properties for most hybrids. Each newly synthesized compound was characterized by IR, 1H NMR, 13C NMR, 31P NMR spectral studies and also HRMS. The results of this study suggest that α-aminophosphonate-tetrahydroisoquinoline hybrids can be promising lead compounds in the discovery of new and improved drugs for the treatment of Alzheimer's disease and related neurodegenerative disorders. [ABSTRACT FROM AUTHOR]