QSAR, docking, dynamic simulation and quantum mechanics studies to explore the recognition properties of cholinesterase binding sites

Correa‐Basurto, José; Bello, Martiniano; Rosales‐Hernández, Martha Cecilia; Hernández-Rodríguez, Maricarmen; Nicolás–Vázquez, María Inés; Rojo‐Domínguez, Arturo; Trujillo‐Ferrara, José G.; Miranda, René; Flores-Sandoval, César A.

doi:10.1016/j.cbi.2013.12.001

Cited by 30 publications

(9 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The electron‐rich environment is due to hyperconjugation through the double bond between carbon atoms 8 and 9 in C7, which promotes an efficient π–π interaction with Tyr124 and increases the attraction between the ligand and protein. This property may be related to the better interaction and higher affinity (Correa‐Basurto et al, ) of C7 for the receptor and therefore a greater disruption in the functioning of the target enzyme (Correa‐Basurto et al, ; Khan et al, ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory

Ciprés-Flores

Farfán‐García

Andrade‐Jorge

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.

show abstract

Section: Discussionmentioning

confidence: 99%

“…According to the theoretical K i , the affinity was propranolol > C8 > galantamine > C7, while based on in vitro assays, it was C8 > galantamine > C7 > propranolol. In silico simulations have been consistently reliable with regard to the binding site, but not affinity values (Correa‐Basurto et al, ).…”

Section: Discussionmentioning

confidence: 99%

Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory

Ciprés-Flores

Farfán‐García

Andrade‐Jorge

et al. 2019

Drug Development Research

View full text Add to dashboard Cite

show abstract

“…The human metabolism of the studied molecules was studied using MetaPrint2D-Reaction, a xenobiotic metabolism prediction software based on data-mining and statistical analysis of known metabolic transformations reported in the scientific literature [ 35 , 37 , 74 , 75 , 76 , 77 , 78 ]. The corresponding results are displayed as circular coloured marks that predict the reactions at that site and the reaction types, to show the metabolite formed.…”

Section: Methodsmentioning

confidence: 99%

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids

et al. 2017

View full text Add to dashboard Cite

The structure of the ortho-, meta- and para- hybrid diindolylmethane-phenylboronic acids and their interactions were optimized with by a quantum chemical method, using density functional theory at the (DFT) level. Thus, infrared bands were assigned based on the scaled theoretical wavenumbers by correlating the respective experimental data of the molecules. In addition, the corresponding 1H-/13C-/11B-NMR experimental and theoretical chemical shifts were correlated. The target molecules showed a poor treatment of the OH shifts in the GIAO method due to the absence of explicit solvent effects in these calculations; therefore, they were explicitly considered with acetone molecules. Moreover, the electron density at the hydrogen bond critical point increased, generating stabilization energy, from weak to moderate or weak to strong, serving as an indicator of the strength of the hydrogen bond between the different intermolecular interactions. Finally, some properties related to the reactive behavior of the target molecules associated with their cytotoxic effects and metabolic pathways were also calculated.

show abstract

“…Grover et al studied 27 flavonoid derivatives by 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations, and used the results to create useful guides to designing AChE inhibitors [16]. Correa et al studied 84 N-aryl-monosubstituted derivatives by 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations, which led them to provide helpful advice regarding the design of acetylcholinesterase and butyrylcholinesterase inhibitors [17]. It should be noted that the above studies could be improved upon by performing similar investigations with more compounds.…”

Section: Introductionmentioning

confidence: 98%

Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer’s disease

Zhou

Wang

et al. 2015

J Mol Model

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).

show abstract

QSAR, docking, dynamic simulation and quantum mechanics studies to explore the recognition properties of cholinesterase binding sites

Cited by 30 publications

References 63 publications

Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory

Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids

Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer’s disease

Contact Info

Product

Resources

About