57041-52-8Relevant academic research and scientific papers
C-H functionalization of azines. Anodic dehydroaromatization of 9-(hetero)aryl-9,10-dihydroacridines
Shchepochkin,Chupakhin,Charushin,Steglenko,Minkin,Rusinov,Matern
, p. 77834 - 77840 (2016)
Data on anodic dehydroaromatization of 9,10-dihydroacridines, bearing aryl and heteroaryl fragments, are presented. Effects of both electron-donating and electron-withdrawing substituents on the current-voltage characteristics of these compounds have been established. The experimental data proved to be in a good agreement with quantum chemical calculations. A simple and convenient method for the electrochemical conversion of dihydroacridines into the corresponding 9-(hetero)aryl-N-methylacridinium salts has been advanced.
9-Substituted acridine derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors possessing antioxidant activity for Alzheimer's disease treatment
Makhaeva, Galina F.,Lushchekina, Sofya V.,Boltneva, Natalia P.,Serebryakova, Olga G.,Rudakova, Elena V.,Ustyugov, Alexey A.,Bachurin, Sergey O.,Shchepochkin, Alexander V.,Chupakhin, Oleg N.,Charushin, Valery N.,Richardson, Rudy J.
, p. 5981 - 5994 (2017)
We investigated the inhibitory activity of 4 groups of novel acridine derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) using the methods of enzyme kinetics and molecular docking. Antioxidant activity of the compounds was determined using the 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS[rad]+) radical decolorization assay as their ability to scavenge free radicals. Analysis of the esterase profiles and antiradical activities of the acridine derivatives showed that 9-aryl(heteroaryl)-N-methyl-9,10-dihydroacridines have a high radical-scavenging activity but low potency as AChE and BChE inhibitors, whereas 9-aryl(heteroaryl)-N-methyl-acridinium tetrafluoroborates effectively inhibit cholinesterases but do not exhibit antiradical activity. In contrast, a group of derivatives of 9-heterocyclic amino-N-methyl-9,10-dihydroacridine has been found that combine effective inhibition of AChE and BChE with rather high radical-scavenging activity. The results of molecular docking well explain the observed features in the efficacy, selectivity, and mechanism of cholinesterase inhibition by the acridine derivatives. Thus, in a series of acridine derivatives we have found compounds possessing dual properties of effective and selective cholinesterase inhibition together with free radical scavenging, which makes promising the use of the acridine scaffold to create multifunctional drugs for the therapy of neurodegenerative diseases.
The tightness contribution to the Bronsted α for hydride transfer between NAD+ analogues
Lee, In-Sook Han,Chow, Kim-Hung,Kreevoy, Maurice M.
, p. 7755 - 7761 (2007/10/03)
It has been shown that the rate of symmetrical hydride transfer reaction varies with the hydride affinity of the (identical) donor and acceptor. In that case, Marcus theory of atom and group transfer predicts that the Bronsted α depends on the location of the substituent, whether it is in the donor or the acceptor, and the tightness of the critical configuration, as well as the resemblance of the critical configuration to reactants or products. This prediction has now been confirmed for hydride transfer reactions between heterocyclic, nitrogen-containing cations, which can be regarded as analogues of the enzyme cofactor, nicotinamide adenine dinucleotide (NAD+). A series of reactions with substituents in the donor gives Bronsted α of 0.67 ± 0.03 and a tightness parameter, τ of 0.64 ± 0.06. With substituents in the acceptor α = 0.32 ± 0.03 and τ = 0.68 ± 0.08. The reactions are all spontaneous, with equilibrium constants between 0.4 and 3 x 104, and the two sets span about the same range of equilibrium constants. The two τ values are essentially identical with an average value of 0.66 ± 0.05. These results can be semiquantitatively mimicked by rate constants calculated for a linear, triatomic model of the reaction. Variational transition state theory and a physically motivated but empirically calibrated potential function were used. The computed rate constants generate an α value of 0.56 if the hydride affinity of the acceptor is varied and an α of 0.44 if the hydride affinity of the donor is varied. The calculated kinetic isotope effects are similar to the measured values. A previous error in the Born charging term of the potential function has been corrected. Marcus theory can be successfully fitted to both the experimental and computed rate constants, and appears to be the most compact way to express and compare them. The success of the linear triatomic model in qualitatively reproducing these results encourages the continued use of this easily conceptualized model to think about group, ion, and atom transfer reactions.
