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.
where 0, λ > 0 are parameters and fC2[0, ∞) such that f(0) < 0. In this paper we study for the cases p (0, β) and p (β, θ) (p is the value of the solution at x = 0 and β, θ are such that f(β) = 0, , the relation between λ and the number of interior critical points of the positive solutions of the above system. 相似文献
Polyfunctional quinolines were synthesized using Friedlander method catalyzed by molecular iodine in high yields at 60 °C under solvent‐free conditions. 相似文献
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. 相似文献
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. 相似文献
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. 相似文献
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. 相似文献
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 pKa 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. 相似文献