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.
The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic
kidney cells expressing only δ opioid receptors. Activation profiles of most of these ligands at δ opioid receptors had not
been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production. 相似文献
Efficient synthesis of ferrocenylenones using a Friedel-Crafts acylation reaction is described. Acryloyl, methacryloyl, crotonoyl, cinnamoyl, and β-methylcrotonoyl chlorides react with ferrocene in the presence of a Lewis acid (EtAlCl2 or EtAlCl2-Me3Al) to give the corresponding ferrocenylenones (acryloyl, methacryloyl, crotonoyl, cinnamoyl, and methylcrotonoylferrocenes) in good isolated yields. Besides ferrocenylenones, chloroactylferrocene is also synthesised by this method. 相似文献
With the decrease in size of devices, rapid characterization of nano-devices is an inevitable necessity. It is shown that Mössbauer spectroscopy using synchrotron radiation from the advanced photon source provides such a tool of investigation. Results are presented and compared for conventional Mössbauer and Nuclear Forward Scattering for 151Eu-doped magnesium sulfide as an example, especially at low concentrations. 相似文献
This paper proves that any set of n points in the plane contains two points such that any circle through those two points encloses at least
points of the set. The main ingredients used in the proof of this result are edge counting formulas for k-order Voronoi diagrams and a lower bound on the minimum number of semispaces of size at most k.Work on this paper by the first author has been supported by Amoco Fnd. Fac. Dev. Comput. Sci. 1-6-44862 and by the National Science Foundation under Grant CCR-8714565, by the second author has been partially supported by the Digital Equipment Corporation, by the fourth author has been partially supported by the Office of Naval Research under Grant N00014-86K-0416. 相似文献
The title compound, C11H10N3+·Cl?·H2O, belongs to the N1‐methyl‐substituted imidazo[4,5‐f]quinoline family, in which the heterocyclic ring is protonated at the pyridine rather than at the imidazole N atom. The molecule as a whole is almost exactly planar. The molecular structure has been compared with that of the 2‐amino analogue described in the literature, and it was found that the extra amino group of the latter is involved in conjugation with the adjacent double bond, i.e. the conjugation does not extend over the entire heterocyclic system. The cation of the title compound forms a strong hydrogen bond with the Cl? anion and the anions are interconnected by the water solvent molecule. 相似文献
Laser light is used for two-step photoionization of Na2. the first step depends on the moleculer orientation, the second step doesnot. This yields a method for the analysis of molecular alignment. 相似文献
Chemical effects on Kβ/Kα X-ray intensity ratios for some Ti, V, Cr, Mn, Fe, Co, Ni, Cu and Zn compounds are studied experimentally. The X-ray spectra were measured by using a Si (Li) solid state detector with high resolution. The vacancies were produced by heavily filtered 241Am gamma rays. It is found that the Kβ/Kα X-ray intensity ratios measured with compounds deviated up to 43% from the corresponding values of the pure elements. The values for pure elements are compared with the other experimental and with theoretical values. 相似文献