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 zinc coordination polymer derived from pyridine-2,6-dicarboxylate (PDC), {[Zn2(PDC)2]}n, was successfully prepared via conventional, sonication and microwave-irradiation methods. The composition and characteristics of the obtained coordination polymers (CPs) were investigated by elemental analysis, TGA/DTA, X-ray diffraction and spectroscopic techniques. The so obtained CPs were heat-treated in the air at 600 °C for 2 h to produce ZnO of nanosized particles (NPs). It is of interest to note that the synthesis approach of the precursor greatly affects both the nanoparticle size and the structure of the resulting ZnO NPs. Moreover, the smallest particle size was associated with the sample derived from the ultrasonically prepared precursor. TEM analysis revealed that all samples have sphere-like morphologies. Structural analysis of the prepared ZnO samples was conducted and compared using Rietveld analysis of their PXRD patterns. Optical band gap calculations based on analysis of the UV–vis spectra of ZnO samples using Tauc's power law were achieved. The highest band gap of 3.63 eV was observed for ZnO sample obtained from the ultrasonically prepared precursor. Furthermore, the photocatalytic activity of ZnO NPs for the removal of Eosin Y color was monitored. The highest removal efficiency was recorded for ZnO originated from the ultrasonically synthesized precursor. Enhancement of removal efficiency that reached 98% was attained in only a period of 8 min. Its recycling test showed that it can be reused without structural changes over four cycling experiments. 相似文献
Decisions concerning a project’s expedition, traditionally involved considerations regarding time and cost tradeoff. It was recently suggested that the quality of a project should also be taken into considerations. In this paper, we propose a meta-heuristic solution procedure for the discrete time, cost and quality tradeoff problem. This problem involves the scheduling of project activities in order to minimize the total cost of the project while maximizing the quality of the project and also meeting a given deadline. We apply a so called electromagnetic scatter search to solve this problem. In this process, we initially generate a population of feasible solutions. In so doing, we use frequency memory to well sample the feasible region. A number of these solutions are then selected and improved locally. The improved solutions are then combined to generate new set of solutions. The combination process utilizes attraction–repulsion mechanisms borrowed from the electromagnetism theory. The whole process is stopped when no significant improvement in the set of solutions are observed. The validity of the proposed solution procedure is demonstrated, and its applicability is tested on a randomly generated large and complex problem having 19,900 activities. 相似文献
This paper is concerned with the spectral analysis of a one-velocity transport operator with Maxwell boundary condition in
L1-space. After a detailed spectral analysis it is shown that the associated Cauchy problem is governed by a C0-semigroup. Next, we discuss the irreducibility of the transport semigroup. In particular, we show that the transport semigroup
is irreducible. Finally, a spectral decomposition of the solutions into an asymptotic term and a transient one which will
be estimated for smooth initial data is given. 相似文献
The effect of atomic hydrogen on the electronic structure of α-titanium samples is studied using the electron-positron annihilation methods. It is shown that different states of hydrogen atoms are manifested in different ways in the positron lifetime distribution spectrum. The results of theoretical calculations of the first component of the positron lifetime are in accord with the obtained experimental data. 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
Theoretical and Mathematical Physics - We study how the entanglement entropy of the Hawking radiation derived using the island recipe for the Reissner–Nordström black hole behaves as the... 相似文献
Complexes of 1,10-o-phenanthroline (o-phen)-NiII and CuII with dithiocarbamates derived from -amino acids (glycine, phenylalanine, alanine, methionine and tryptophan) were synthesized and characterized by chemical analysis, spectral and thermal studies and by biological screening; the complexes are non-electrolytes. The empirical formula are [Ni(o-phen)2(aadtc)] and [Cu2(o-phen)2(phaladtc)(H2O)2Br2] where, aadtc = glycinyl-, phenylalaninyl-, alaninyl-, methioninyl- and tryptophanyldithiocarbamate and phaladtc = phenylalaninyldithiocarbamate. The structure of these complexes is probably octahedral. Molecular association through hydrogen bonding between the —NH and the carboxylate groups is proposed for the NiII complexes. The CuII complex is dimeric with the phenylalaninyldithiocarbamate acting as a bridge. 相似文献
Summary Mixed ligand complexes of the type K[Cu(x-HQA)Rxan] [x-HQA = 5-arylazo-8-hydroxyquinoline derivatives; Rxan = methyl or ethylxanthate] have been prepared and characterised by elemental analysis, spectral measurements and conductivity. Upon irradiation, solutions of these complexes photoeliminate dinitrogen and a mechanism for this reaction is proposed. The photosensitivity of the oxine ligand was found to be responsible for the observed photolysis of the complexes. 相似文献