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.

     

A new, efficient, and simple method for the synthesis of thiiranes from epoxides under solvent-free conditions

A simple, efficient, and new method has been developed for the synthesis of thiiranes from epoxides through a one-pot reaction of epoxides with diethyl phosphite in the presence of ammonium acetate or ammonium hydrogen carbonate/sulfur/ and acidic alumina under solvent-free conditions using microwave irradiation.     

Electrochemical platform for simultaneous determination of levodopa,acetaminophen and tyrosine using a graphene and ferrocene modified carbon paste electrode

Microchimica Acta - A carbon paste electrode (CPE) was modified with graphene and ethyl 2-(4-ferrocenyl-[1,2,3]triazol-1-yl) acetate (EFTA) and used for electrocatalytic oxidation of levodopa....     

Phyto-synthesis of silver nanoparticles using aerial extract of Salvia leriifolia Benth and evaluation of their antibacterial and photo-catalytic properties

Research on Chemical Intermediates - We have synthesized silver nanoparticles (Ag-NPs) via a simple and eco-friendly method through the utilization of aqueous aerial parts of Salvia leriifolia...     

Inside-Needle Extraction Method Based on Molecularly Imprinted Polymer for Solid-Phase Dynamic Extraction and Preconcentration of Triazine Herbicides Followed by GC–FID Determination

An inside-needle extraction method was developed through thermal polymerization of atrazine-molecularly imprinted polymer (MIP) on the internal surface of a stainless steel hollow needle, which was oxidized and silylated. The fabricated coating (MIP layer) for the needle was durable and showed very good chemical and thermal stability. It could be mounted on a glass syringe and be directly coupled with gas chromatographic (GC) systems. The parameters being effective on the coating and extraction processes, namely nature of oxidizing agent, silylation time, nature and amount of porogen, template-to-MIP components ratio, polymerization time and temperature, sample volume, flow rate, pH and ionic strength of the sample were investigated and optimized. The extraction needle showed high selectivity as well as a great extraction capacity for triazines. The extraction of atrazine, simazine, cyanazine, ametryn, prometryn and terbutryn using the fabricated extraction needle and followed by GC analysis resulted in detection limits of 2.6, 21, 24, 32, 38 and 42 ng mL⁻¹, respectively. The fabricated needle proved to be applicable to the analysis of real samples by comparing the results obtained for non-spiked and spiked samples of grape juice, tap water and groundwater.

     

CFD Simulation of Rheological Model Effect on Cuttings Transport

Foam, as a non-Newtonian fluid, plays an important role in the underbalanced drilling technique in oil field development. The rheological properties of drilling fluids, such as foam, have a direct effect on flow characteristics and hydraulic performance. Two rheological models—the Herschel–Bulkley model and power law—were fitted to two foam systems in this study. Computational fluid dynamics (CFD) was used to simulate the effect of the rheological models on solid–liquid (cuttings transport) hydraulics in concentric and eccentric annulus during the foam drilling operation. The simulation results are compared to the experimental data from previous studies. The results of CFD using the power law model are in good agreement with experimental results in horizontal annulus with respect to the Herschel–Bulkley model with relative error less than 8%. Thus, for CFD cuttings transport for simulations in inclined and horizontal annulus, it is best to use the power law's rheological model parameters.     

Complexes with Atomic Gold Ions: Efficient Bis-Ligand Formation

Complexes of atomic gold with a variety of ligands have been formed by passing helium nanodroplets (HNDs) through two pickup cells containing gold vapor and the vapor of another dopant, namely a rare gas, a diatomic molecule (H₂, N₂, O₂, I₂, P₂), or various polyatomic molecules (H₂O, CO₂, SF₆, C₆H₆, adamantane, imidazole, dicyclopentadiene, and fullerene). The doped HNDs were irradiated by electrons; ensuing cations were identified in a high-resolution mass spectrometer. Anions were detected for benzene, dicyclopentadiene, and fullerene. For most ligands L, the abundance distribution of AuL_n⁺ versus size n displays a remarkable enhancement at n = 2. The propensity towards bis-ligand formation is attributed to the formation of covalent bonds in Au⁺L₂ which adopt a dumbbell structure, L-Au⁺-L, as previously found for L = Xe and C₆₀. Another interesting observation is the effect of gold on the degree of ionization-induced intramolecular fragmentation. For most systems gold enhances the fragmentation, i.e., intramolecular fragmentation in AuL_n⁺ is larger than in pure L_n⁺. Hydrogen, on the other hand, behaves differently, as intramolecular fragmentation in Au(H₂)_n⁺ is weaker than in pure (H₂)_n⁺ by an order of magnitude.     

Size‐Mediated Recurring Spinel Sub‐nanodomains in Li‐ and Mn‐Rich Layered Cathode Materials

Li‐ and Mn‐rich layered oxides are among the most promising cathode materials for Li‐ion batteries with high theoretical energy density. Its practical application is, however, hampered by the capacity and voltage fade after long cycling. Herein, a finite difference method for near‐edge structure (FDMNES) code was combined with in situ X‐ray absorption spectroscopy (XAS) and transmission electron microscopy/electron energy loss spectroscopy (TEM/EELS) to investigate the evolution of transition metals (TMs) in fresh and heavily cycled electrodes. Theoretical modeling reveals a recurring partially reversible LiMn₂O₄‐like sub‐nanodomain formation/dissolution process during each charge/discharge, which accumulates gradually and accounts for the Mn phase transition. From the modeling of spectra and maps of the valence state over large regions of the cathodes, it was found that the phase change is size‐dependent. After prolonged cycling, the TMs displayed different levels of inactivity.     

Effervescent tablet‐assisted demulsified dispersive liquid–liquid microextraction based on solidification of floating organic droplet for determination of methadone in water and biological samples prior to GC‐flame ionization and GC‐MS

A novel effervescent tablet‐assisted demulsified dispersive liquid–liquid microextraction based on the solidification of floating organic droplet was developed to determine methadone prior to gas chromatography with flame ionization detection and gas chromatography with mass spectrometry. In this method, a tablet composed of citric acid, sodium carbonate, and 1‐undecanol was utilized. The resulting effervescent tablet generated carbon dioxide in situ to disperse 1‐undecanol in the sample. Thus, the dispersive and extraction processes were performed in one synchronous step. An aliquot of acetonitrile as the demulsifier solvent was used for the separation of two phases instead of centrifugation. Under optimal conditions, the developed method was linear up to 50 000 µg/L with correlation coefficients higher than 0.99. Moreover, limits of detection and limits of the quantification were in the range of 3‐10  and 7‐30 µg/L in water and biological samples, respectively. Intra‐ and interday precisions (n = 6) of the spiked methadone at a concentration level of 50 µg/L were over ranges of 5.1‐6.8% and 5.7‐7.1%, respectively. The preconcentration factors and recovery values were obtained in the range of 140‐145 and 98.1 to 101.6% in real samples, respectively.