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.

     

Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]manganese(III) acetate as a novel carrier for a selective iodide PVC membrane electrode.

[5,10,15,20-Tetrakis(4-N,N-dimethylaminobenzene)porphyrinato]Mn(III) acetate (MnTDPAc) was applied as an ionophore for an iodide-selective PVC membrane electrode. The influences of the membrane composition, pH of the test solution and foreign ions on the electrode performance were investigated. The sensor exhibited not only excellent selectivity to iodide ion compared to Cl- and lipophilic anions such as ClO4- and salicylate, but also a Nernstian response with a slope of -59.4 +/- 1.2 mV per decade for iodide ions over a wide concentration range from 1.0 x 10(-2) to 7.5 x 10(-6) M at 25 degrees C. The potentiometric response was independent of the pH of the solution in the pH range of 2 - 8. The electrode could be used for at least 2 months without any considerable divergence in the potential. Good selectivity for iodide ion, a very short response time, simple preparation and relatively long-term stability were the silent characteristics of this electrode. It was successfully used as an indicator electrode in the potentiometric titration of iodide ions, and also in the determination of iodide from seawater samples and drug formulations.     

Headspace SPME–GC Method for Acetone Analysis and its Biomedical Application

A new method for extraction and analysis of acetone in human urine based on headspace solid phase microextraction using a mixture of activated carbon and zeolite as sorbents in a PVC matrix coated on a silver wire and its application to the determination of ketone bodies is described. Unlike commercial fibers, which are coated on fused silica, the coating adheres strongly to the silver wire and is thermally stable up to 250 °C. After optimization of coating composition and microextraction conditions the fiber was used for the analysis of acetone in human urine.     

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.     

Synthesis of 2,2-Dimethyl-1,2-Dihydro-3H-pyrrol-3-one Preliminary Communication

The title compound 3g is obtained via two different routes, either in a multistep synthesis starting from 2-amino-2-methylpropionic acid (methylalanine) or by light-induced, oxidative dealkylation of the corresponding N-isopropyl derivative 3c .     

Poly(N‐Bromobenzene‐1,3‐Disulfonylamide), N,N,N′,N′‐Tetrabromobenzene‐1,3‐Disulfonylamide and DABCO‐Bromine Complex: As Novel Reagents for the Oxidative Coupling of Thiols to Disulfides

An efficient method for the oxidative coupling of thiols to their corresponding disulfides by new reagents poly(N‐bromobenzene‐1,3‐disulfonylamide) PBBS , N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonylamide TBBDA and DABCO‐bromine complex is described. The reaction was applicable to a variety of thiols with high chemoselectivity.     

Photochemistry of 2-Allyl-3-oxo-2,3-dihydro-1H-pyrrole-2-carboxyalates

On acetone-sensitized irradiation the title compounds 3a–c are converted to 2-allyl-3-hydroxy-1H-pyrrole-2-carboxylates 4 in reasonable yields.