Novel tacrine-based acetylcholinesterase inhibitors as potential agents for the treatment of Alzheimer’s disease: Quinolotacrine hybrids

A new series of quinolotacrine hybrids including cyclopenta- and cyclohexa-quinolotacrine derivatives were designed, synthesized, and assessed as anti-cholinesterase (ChE) agents. The designed derivatives indicated higher inhibitory effect on the acetylcholinesterase (AChE) with IC₅₀ values of 0.285–100 µM compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 µM. Of these compounds, cyclohexa-quinolotacrine hybrids displayed a little better anti-AChE activity than cyclopenta-quinolotacrine hybrids. Compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6m) including 3-hydroxyphenyl and cyclohexane ring moieties exhibited the best AChE inhibitory activity with IC₅₀ value of 0.285 µM. The kinetic and molecular docking studies indicated that compound 6m occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE as a mixed inhibitor. Using neuroprotective assay against H₂O₂-induced cell death in PC12 cells, the compound 6h illustrated significant protection among the assessed compounds. In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these quinolotacrine hybrids can be very encouraging AChE inhibitors to treat Alzheimer’s disease.

Graphic abstract

A novel series of quinolotacrine hybrids were designed, synthesized, and evaluated against AChE and BChE enzymes as potential agents for the treatment of AD. The hybrids showed good to significant inhibitory activity against AChE (0.285–100 μM) compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 μM. Among them, compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c′] diquinolin-6-one (6 m) bearing 3-hydroxyphenyl moiety and cyclohexane ring exhibited the highest anti-AChE activity with IC₅₀ value of 0.285 μM. The kinetic and molecular docking studies illustrated that compound 6 m is a mixed inhibitor and binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

     

Zinc polyoxometalate on activated carbon: an efficient catalyst for selective oxidation of alcohols with hydrogen peroxide

[PW₁₁ZnO₃₉]^5? was immobilized on activated carbon and characterized using Fourier transform infrared, X‐ray diffraction, Brunauer–Emmett–Teller and elemental analysis techniques. Effective oxidation of various alcohols with hydrogen peroxide was performed in the presence of this catalyst. Easy separation of the catalyst from the reaction mixture, cheapness, high activity and selectivity, stability as well as retained activity in subsequent catalytic cycles make this supported catalyst suitable for small‐scale synthesis. Copyright © 2015 John Wiley & Sons, Ltd.     

Rapid and efficient synthesis of 2-imidazolines and bis-imidazolines under ultrasonic irradiation

Rapid and efficient preparation of 2-imidazolines and bis-imidazolines by reaction of ethylenediamine with nitriles in the presence of catalytic amounts of sulfur under ultrasonic irradiation is reported. The advantages of this system are short reaction times, high yields and the ability to carry out large scale reactions.     

Iodine‐Catalyzed Friedlander Quinoline Synthesis under Solvent‐Free Conditions

Polyfunctional quinolines were synthesized using Friedlander method catalyzed by molecular iodine in high yields at 60 °C under solvent‐free conditions.     

Ionic strength dependence of stability constants,complexation of W(VI) with iminodiacetic acid

The equilibria between tungsten(VI) and iminodiacetic acid (IDA) have been studied in aqueous solution. The stoichiometry and stability constants of the complexes formed are determined from a combination of potentiometric and Uv spectroscopic measurements. All measurements are carried out at 25°C, pH 7.5 and different ionic strengths ranging from (0.1 to 1.0) mol dm⁻³ (NaClO₄). According to these results, tungsten(VI) forms a mononuclear complex with IDA of the type (WO₃L²⁻). By introducing two empirical parameters C and D in the complex-formation reaction between tungsten(VI) and IDA, the dependence of the dissociation and stability constants on ionic strength is described by a modified Debye-Huckel-type equation. Finally, a pattern for the ionic strength dependence is obtained.     

Diammonium Hydrogen Phosphate as an Efficient and Inexpensive Catalyst for the Synthesis of Bis(indolyl)methanes under Solvent-Free Conditions

Bis(indolyl)methanes were synthesized by the reaction of indole derivatives and aromatic and aliphatic aldehydes in the presence of diammonium hydrogen phosphate as a solid catalyst under solvent-free conditions. This methodology offers significant improvements for the synthesis of bis(indolyl)methanes with regard to the yield of products, simplicity in operation, and green aspects by avoiding toxic catalysts and solvents.     

A new approach to the facile synthesis of mono- and disubstituted quinazolin-4(3H)-ones under solvent-free conditions

Quinazolin-4(3H)-one derivatives were synthesized successfully via a one-pot, three component reaction of isatoic anhydride and an orthoester with ammonium acetate or a primary amine catalyzed by silica sulfuric acid under solvent-free conditions. This is the first report on the synthesis of 2-substituted quinazolin-4(3H)-ones by this procedure.     

A facile procedure for the one-pot synthesis of unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles

Unsymmetrically 2,5-disubstituted 1,3,4-oxadiazoles were efficiently synthesized from the cyclization-oxidation reaction of acyl hydrazones. Also, the synthesis of the title compounds was achieved by the condensation of acyl hydrazides and aromatic aldehydes in the presence of ceric ammonium nitrate in dichloromethane.     

Spectrophotometric Determination of Acidity Constants of 4‐(2‐Pyridylazo) Resorcinol in Various Micellar Media Solutions

Dissociation equilibria of 4‐(2‐pyridylazo) resorcinol (PAR) in aqueous micellar solutions were determined spectrophotometrically at 25 °C and at the constant ionic strength I = 0.1 M KNO₃. For this purpose, the effect of nonionic (Brij‐35, Triton X‐100, Triton X‐114, Triton X‐405), and anionic (SDS) surfactants on the absorption spectra of PAR at different pH values was studied. Results show that the pK_a values and pure spectra of each species of PAR are influenced by percentages of a neutral and an anionic surfactant such as Brij‐35, Triton X‐100, Triton X‐114, Triton X‐405 and SDS, respectively, added to the solution of this reagent.