Theoretical study of classical acetylcholinesterase inhibitors

Nascimento, Érica C. M.; Martins, João B. L.; Santos, Maria Lucília dos; Gargano, Ricardo

doi:10.1016/j.cplett.2008.05.006

Cited by 22 publications

(13 citation statements)

References 24 publications

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“…3 However, the best treatment currently available for AD is based on a cholinergic hypothesis, which relates the deficit of cognition to the reduction of the neurotransmitter acetylcholine (ACh), that implies the reduction of the neurotransmission process. 5,6 One of the enzymes involved in these biological processes is acetylcholinesterase (AChE), which is capable of regulating the process of neurotransmission and the levels of acetylcholine in the synaptic cleft, since it is able to catalyze the hydrolysis of this neurotransmitter. 7 For this reason, many studies of theoretical and experimental nature have been developed with the purpose of finding compounds with ability to inhibit the enzyme acetylcholinesterase.…”

Section: Introductionmentioning

confidence: 99%

“…7 For this reason, many studies of theoretical and experimental nature have been developed with the purpose of finding compounds with ability to inhibit the enzyme acetylcholinesterase. 6 Thus, the first drugs used for the symptomatic treatment of Alzheimer's disease act in a way to selectively inhibit AChE. In addition to tacrine (which is no longer used) and the potent nicotinic receptors rivastigmine and galantamine, the most prescribed drug donepezil has been widely used in the treatment of AD.…”

Section: Introductionmentioning

confidence: 99%

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Functionalized Dienes: A New Series of Potential Agents for the Treatment of Alzheimer’s Disease

Oliveira¹,

Meier²,

Zapp³

et al. 2019

J. Braz. Chem. Soc.

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We report a series of functionalized dienes as compounds of great potential in the treatment of Alzheimer's disease due to their antioxidant activity and ability to inhibit the enzyme acetylcholinesterase. The dienes tested showed high enzymatic inhibition capacity and accentuated antioxidant activity, which are comparable to or higher than the standards tested. Molecular docking studies were performed to confirm the experimental results. We also describe the correlation values between the antioxidant activity and oxidation potentials. Predicted bioactivity scores and quantum studies were also determined.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functionalized Dienes: A New Series of Potential Agents for the Treatment of Alzheimer’s Disease

Oliveira¹,

Meier²,

Zapp³

et al. 2019

J. Braz. Chem. Soc.

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“…As determined by crystallographic studies, tacrine binds directly and selectively to the active site of AchE without interacting with any other site [8]. Since tacrine displays unusual interaction properties, many computational studies were also reported on tacrine [9][10][11]. Another such molecule is saccharin (1,2benzisothiazol-3(2H)-one-1,1-dioxide, Fig.…”

Section: Introductionmentioning

confidence: 99%

The amidine formed by tacrine and saccharin revisited: An ab initio Investigation of Structural, Electronic and Spectroscopic Properties

Açar

2019

Turkish Computational and Theoretical Chemistry

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Computational study of tacrine and saccharin and their amidine complex (TacSac) was peformed by ab initio calculations including electron correlation. Structure, UV-Vis spectra and charge distribution of the amidine (TacSac) were investigated using ground state geometries optimized at MP2/6-311++G(d,p) level. The effects of solvent was investigated using polarizable continuum model (PCM) in conjunction with the solvation model based on density (SMD) approach. TacSac geometry remained same in gas phase and in H2O both with PCM and SMD models in contrast to former DFT results. The amidine is calculated to be stable indicating that former DFT calculations underestimated the stability of the investigated amidine. UV-Vis spectra and electronic transitions were calculated at CIS/6-311++G(d,p), B3LYP/6-311++G(d,p) and CAM-B3LYP/6-311++G(d,p) levels of theory and B3LYP gave the best results. TacSac has a peak at a higher wavelength enabling S0→S1 transition with a lower energy. S0→S1 transition corresponds to full charge transfer between HOMO and LUMO orbitals of TacSac in H2O. The ab initio results indicate that the TacSac system can be synthesized with an easy condensation reaction, and that the amidine product is a potential candidate for photochemical charge-transfer systems.

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“…A methodology based on PCA for the pharmacophore identification of the acetylcholinesterase inhibitors (AChEI) was recently used (de Paula, 2009;de Paula, 2007;Fang, 2011;Nascimento, 2011;Nascimento, 2008). In this chapter the electronic, structural, topological and chemical properties of studied molecules, were taken from the theoretical procedures and related to the activity by means of the multivariate analysis PCs that provides the pharmacophoric profile of these AChEIs.…”

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confidence: 99%

“…PCA have been used to find new potential molecules in a series of biological systems (Carotti, 2003, de Paula, 2009de Paula, 2007;Li, 2009;Nascimento, 2011;Nascimento, 2008;Rocha, 2011;Steindl, 2005). A methodology based on PCA for the pharmacophore identification of the acetylcholinesterase inhibitors (AChEI) was recently used (de Paula, 2009;de Paula, 2007;Fang, 2011;Nascimento, 2011;Nascimento, 2008).…”

mentioning

confidence: 99%