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.

     

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.     

Sensitivity of the population of states to the value of q and legitimate range of q in Tsallis statistics

In the framework of the Tsallis statistical mechanics, we study the change of the population of states when the parameter q is varied, for some model systems; the results show that the difference between predictions of the Boltzmann-Gibbs and Tsallis statistics can be much smaller than the precision of any existing experiment. Also, the relation between privilege of rare and frequent events and the value of q is restudied. It is shown that positive q privilege frequent and negative q privilege rare events. Finally, the convergence criteria of the partition function of some simple model systems, in the framework of Tsallis statistical mechanics, is studied. Based on this study, we conjecture that q = 1, in the thermodynamic limit.     

The first report on the catalytic oxidation of urazoles to their corresponding triazolinediones via in situ catalytic generation of Br using periodic acid or oxone/KBr system

A combination of periodic acid or oxone^® and a catalytic amount of KBr in the presence of few drops of water, were used for the catalytic oxidation of urazoles and bis-urazoles to their corresponding triazolinediones under mild and heterogeneous conditions with moderate to excellent yields.     

Melamine-(H_2SO_4)_3 and PVP-(H_2SO_4)_n as solid acids:Synthesis and application in the first mono-and di-nitration of bisphenol A and other phenols

Melamine and poly vinylpyrrolidone（PVP） reacted with neat sulfuric acid readily to form two new organic solid acids namely melamine-（H₂SO₄）₃ and PVP-（H₂SO₄）_n.These solid acids were used for the first nitration of bisphenol A as well as other phenols in the presence of NH₄NO₃.Mono- and di-nitro bisphenol A have been characterized with IR and ¹H NMR techniques.     

Effect of model potential of adsorptive bond on the thermodynamic properties of adsorbed CO molecules on Ni(111) surface

The effect of anharmonicity on the adsorption of CO molecules on the Ni(111) surface has been investigated. The DFT calculations are used to obtain the effective adsorption potential of the CO molecule on the Ni(111) surface. First, using an appropriate slab model, the geometry of adsorption system corresponding to hcp, fcc, bridge, and on-top sites with p(2 x 2) arrangement and coverage of 0.25 ML is optimized by the DFT calculations using a plane wave basis set and ultrasoft pseudopotentials; this gives the hcp site as the most stable site with De = 185 kJ/mol, for which the equilibrium distance of CO from the surface and C-O bond length on the surface are found to be 1.31 and 1.192 A, respectively. Then, the potential function of adsorption versus adsorptive bond distance was plotted, which is significantly different from that of a harmonic oscillator, i.e., the anharmonicity for the adsorptive bond is significant. Also the harmonic and anharmonic shifts of vibrational frequencies of adsorptive and C-O bonds are calculated to be -22.6 and 7.8 cm(-1), respectively. Hence, two potential models are selected for which their Schr?dinger equations are solved analytically, namely the hard repulsion-soft attraction (HS) and Morse potential (MP) models. The adsorption isotherms, internal energy, isochoric heat capacity, and entropy of adsorbed CO molecules have been calculated for the mentioned model potentials and compared with those of the harmonic oscillator (H). As a result, the adsorption isotherms are not considerably sensitive to the model potential. The anharmonicity of CO-Ni bond, which is included in HS and MP models, gives an average deviation in pressure as much as 1.4% for HS and 5.8% for MP, compared to 6.1% for the H model. However, isochoric heat capacity and entropy depend on the model potential significantly, and the differences may be as high as 69% and 55% for isochoric heat capacity and entropy, respectively.     

N2O4 Chemisorbed onto n‐Propylsilica Kryptofix 21 and Kriptofix 22 as Two New Functional Polymers for the Fast Oxidation of Urazoles and 1,4‐Dihydropyridines

3‐Chloropropylsilica was reacted with Kriptofix 21 or 22 in the presence of triethylamine to form N‐propylsilica Kryptofix 21 and Kriptofix 22. Then N₂O₄ was added to each of these polymers to chemisorb onto cavity of aza‐crown ethers. These functionalized polymers were applied for the fast and simple oxidation of urazoles and 1,4‐dihydropyridines, respectively.     

{[K.18-Crown-6]Br3}n:保护胺和醇的三溴化催化剂（英文）

{[K.18-Crown-6]Br3}n , a unique tribromide-type catalyst, was utilized for the N-boc protection of amines and trimethylsilylation (TMS) and tetrahydropyranylation (THP) of alcohols. The method is general for the preparation of N-boc derivatives of aliphatic (acyclic and cyclic) and aromatic, and primary and secondary amines and also various TMS-ethers and THP-ethers. The simple separation of the catalyst from the product is one of the many advantages of this method.