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Isolation of silymarin, a mixture of well-defined flavonolignans, from the seeds of milk thistle (Silybum marianum) was achieved. Silymarin was extracted from defatted seed with acetone without heating; the yield was Y=4.1 %. The antioxidant activity of silymarin was determined at ambient temperature by means of a 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetry with a detection scheme at Λ= 515 nm. The activity was evaluated by the decrease in absorbance as the result of a DPPH radical color change from purple to yellow. The results obtained showed that ascorbic acid was a substantially more powerful antioxidant than silymarin, but silymarin was a significantly stronger quencher of DPPH radical than the standard silibinin.

It is an exceptional challenge to perform organic reactions in water. In the last decade, scientific research in the field of water as a green solvent has continued to grow exponentially. Apart from being cheap, water is harmless to the environment and sometimes gives completely unexpected reactivity in reactions. There is a wide range of organic reactions that can take place in water: from common oxidation-reduction reactions, reactions involving carbocations and carbocations, pericyclic reactions, transition metal reactions, and others. Organic reactions in an aqueous medium are used in the chemistry of carbohydrates and in the chemical modification of biomolecules. More recently, water has been used as a medium in microwave synthesis. This review gives an insight into the importance of this field, since organic reactions in water as a solvent, take place according to the principles of green chemistry. [ABSTRACT FROM AUTHOR]

In the conventional method, the most effective DESs were: choline chloride:thiourea, choline chloride:oxalic acid, and choline chloride:levulinic acid, but none of these provided high yields. The most effective eutectic solvents in this method were choline chloride:oxalic acid and choline chloride:levulinic acid. The most effective eutectic solvents for the quaternization of pyridoxal oxime with substituted 2-bromoacetophenones in the ultrasonic method were choline chloride:oxalic, choline chloride:levulinic acid and choline chloride: I trans i -cinnamic acid. Yields (%) of the compounds 3f, 3g and 3i obtained by conventional (blue), microwave (orange) and ultrasonic (grey) method in three eutectic solvents (choline chloride/oxalic acid, choline chloride/levulinic acid and choline chloride/trans-cinnamic acid). [Extracted from the article]

The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and N -acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of β-amyloid plaques by inhibiting both the β-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants ( K i) in micromolar range able to lower the activity of β-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants. Also, most of them were estimated to be able to cross the blood-brain barrier by passive transport and to be absorbed in human intestines as well as with moderate metabolic stability in liver microsomes.

Seven pyridoxal dioxime quaternary salts ( 1 - 7 ) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal monooxime with substituted 2-bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43-76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes ( K i = 100-400 µM). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon-inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).

The Menshutkin reaction represents the alkylation of tertiary amines by alkyl halide where the reactants are neutral and the products, quaternary ammonium salts, are two ions with opposite signs. The most commonly used organic solvents in quaternization reactions are volatile organic solvents (VOSs), namely acetone, anhydrous benzene, dry dichloromethane (DCM), dimethylformamide (DMF) and acetonitrile (ACN). The purpose of this work was to examine eutectic solvents as a "greener" alternative to conventional solvents so that quaternization reactions take place in accordance with the principles of green chemistry. Herein, sixteen eutectic solvents were used as replacements for volatile organic ones in quaternization reactions of isonicotinamide with substituted phenacyl bromides. The reactions were carried out at 80 °C by three synthetic approaches: conventional (4-6 h), microwave (20 min) and ultrasound (3 h). Microwave-assisted organic reactions produced the highest yields, where in several reactions, the yield was almost quantitative. The most suitable eutectic solvents were based on choline chloride (ChCl) as the hydrogen bond acceptor (HBA) and glycerol, oxalic or levulinic acid as hydrogen bond donors (HBDs). The benefits of these three deep eutectic solvents (DESs) as a medium for quaternization reactions are the simplicity of their preparation for large-scale production, with inexpensive, available and nontoxic starting materials, as well as their biodegradability.

We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds reversibly inhibited both enzymes in the micromolar range pointing to the preference of AChE over BChE for binding the tested derivatives. Molecular docking studies revealed the importance of interactions with AChE active site residues Tyr337 and Tyr124, which dictated most of the observed differences. The most potent inhibitor of both enzymes with K i of 4 μM for AChE and 8 μM for BChE was the nicotinamide derivative 1-(4'-phenylphenacyl)-3-carbamoylpyridinium bromide. Such a result places it within the range of several currently studied novel cholinesterase inhibitors. Cytotoxicity profiling did not classify this compound as highly toxic, but the induced effects on cells should not be neglected in any future detailed studies and when considering this scaffold for drug development.

The quaternization reactions of nicotinamide, with different electrophiles: methyl iodide and substituted 2-bromoacetophenones (4-Cl, 4-Br, 4-H, 4-CH₃, 4-F, 4-OCH₃, 4-Ph, 2-OCH₃, 4-NO₂) are reported. The preparations were carried out by conventional synthesis and under microwave irradiation in absolute ethanol and acetone. The synthesis performed by microwave dielectric heating significantly improved yield, up to 8 times, and shortened down the reaction time from ca. one day in conventional, to 10⁻20 min. The structures of the synthesized compounds were confirmed by IR, ¹H- and 13 C-NMR spectroscopy, mass spectrometry and elemental analysis. The compounds have been screened for antifungal activities against Fusarium oxysporum , Fusarium culmorum , Macrophomina phaseolina and Sclerotinia sclerotiorum at concentrations of 10 µg/mL and 100 µg/mL. Six compounds showed the strong inhibition of mycelium growth at a concentration of 10 µg/mL. All tested compounds revealed the great inhibitory activities against S. sclerotiorum at a concentration of 100 µg/mL., Competing Interests: The authors declare no competing financial interest.

Organophosphorus (OP) nerve agents (sarin, tabun VX and soman) inhibit the enzyme acetylcholinesterase (AChE, EC 3.1.1.7) by binding to its active site while preventing neurotransmission in the cholinergic synapses. The protection and treatment of this kind of poisoning are still a challenge as we are yet to discover an antidote that would be effective in all cases of poisoning. To aid the search for more efficient antidotes, we evaluated the ability of nine pyridoxal oxime derivatives, prepared by a novel synthetic pathway, to reactivate recombinant human AChE and the related purified human plasma butyrylcholinesterase (BChE, EC 3.1.1.8) inhibited by VX, tabun and paraoxon. Oximes are derivatives of vitamin B6 bearing a phenacyl moiety attached to the quaternary nitrogen atom and having various substituents on the phenyl ring. As the results have shown, the tested oximes were in general more efficient in the reactivation of OP-inhibited BChE than AChE. The highest observed rate was in the case of VX-inhibited BChE reactivation, where k obs was 0.0087min -1 and the reactivation maximum of 90% was achieved within 5h. The cholinesterases displayed a binding affinity for these derivatives in a μmolar range no matter the substituent on their rings which was in accordance with the molecular modelling results showing a similar binding pattern for all oximes within the active site of both AChE and BChE. Such a positioning reveals also that hydroxy and a metoxy substituents at the vicinity of the oxime moiety present a possible steric hindrance explaining the reactivation results., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Quaternary salts of pyridoxal oxime have been synthesized by the quaternization of pyridoxal oxime with substituted phenacyl bromides using microwave heating. Microwave-assisted rapid synthesis was done both in solvent (acetone) and under solvent-free conditions. Good to excellent yields (58%-94%) were obtained in acetone in very short reaction times (3-5 min) as well as in the solvent-free procedure (42%-78%) in very short reaction times (7-10 min) too. Effective metodologies for the preparation of pyridoxal oxime quaternary salts, having the advantagies of being eco-friendly, easy to handle, and performed in shorter reactions time are presented. The structure of compound 7, in which a 4-fluorophenacyl moiety is bonded to the pyridinium ring nitrogen atom, was unequivocally confirmed by the single-crystal X-ray diffraction method.