Last update 01 Nov 2024

CEL x AChE

Last update 01 Nov 2024

Basic Info

Related Targets

CELAChE

Drugs associated with CEL x AChE

Cholesterol esterase and acetylcholinesterase inhibition(University of Bonn)

Target

AChE x CEL

Mechanism

AChE inhibitors [+1]

Active Org.

University of Bonn

Originator Org.

University of Bonn

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CEL x AChE

100 Translational Medicine associated with CEL x AChE

0 Patents (Medical) associated with CEL x AChE

Literatures (Medical) associated with CEL x AChE

01 Feb 2023·Molecular Neurobiology

Long-Lasting Impact of Sugar Intake on Neurotrophins and Neurotransmitters from Adolescence to Young Adulthood in Rat Frontal Cortex

Article

Author: Troise, Antonio Dario ; Spagnuolo, Maria Stefania ; Mazzoli, Arianna ; Gatto, Cristina ; Tonini, Claudia ; Cigliano, Luisa ; Iossa, Susanna ; Nazzaro, Martina ; Scaloni, Andrea ; Pallottini, Valentina ; Segatto, Marco ; Colardo, Mayra

AbstractThe detrimental impact of fructose, a widely used sweetener in industrial foods, was previously evidenced on various brain regions. Although adolescents are among the highest consumers of sweet foods, whether brain alterations induced by the sugar intake during this age persist until young adulthood or are rescued returning to a healthy diet remains largely unexplored. To shed light on this issue, just weaned rats were fed with a fructose-rich or control diet for 3 weeks. At the end of the treatment, fructose-fed rats underwent a control diet for a further 3 weeks until young adulthood phase and compared with animals that received from the beginning the healthy control diet. We focused on the consequences induced by the sugar on the main neurotrophins and neurotransmitters in the frontal cortex, as its maturation continues until late adolescence, thus being the last brain region to achieve a full maturity. We observed that fructose intake induces inflammation and oxidative stress, alteration of mitochondrial function, and changes of brain-derived neurotrophic factor (BDNF) and neurotrophin receptors, synaptic proteins, acetylcholine, dopamine, and glutamate levels, as well as increased formation of the glycation end-products Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL). Importantly, many of these alterations (BDNF, CML, CEL, acetylcholinesterase activity, dysregulation of neurotransmitters levels) persisted after switching to the control diet, thus pointing out to the adolescence as a critical phase, in which extreme attention should be devoted to limit an excessive consumption of sweet foods that can affect brain physiology also in the long term.

01 Jan 2019·ToxicologyQ3 · MEDICINE

X-ray structures of human bile-salt activated lipase conjugated to nerve agents surrogates

Q3 · MEDICINE

Article

Author: Touvrey, Cédric ; Nachon, Florian ; Terreux, Raphael ; Courageux, Charlotte ; Guillon, Virginia ; Brazzolotto, Xavier

The efficiency of human butyrylcholinesterase (BChE) as a stoichiometric bioscavenger of nerve agents is well established. However, wide use is currently limited by production and purification costs. Aiming at identifying an alternative human protein bioscavenger, we looked for an original scaffold candidate by virtual screening of the Protein Data Bank for functional similarity using the "Surfing the Molecules" software (sumo-pbil.ibcp.fr) and a search model based on the BChE active site topology. Besides the expected acetylcholinesterase and butyrylcholinesterase, we identified a set of bile salt activated lipases structures, among which the human pancreatic lipase (hBAL) that shares 34% identity with BChE. We produced the recombinant enzyme in mammalian cells, purified it, and measured the inhibition constants for paraoxon and surrogates of VX, sarin and tabun. We solved the X-ray structure of apo hBAL and conjugates with paraoxon and the surrogates at resolutions in the 2-Å range. These structures allow the assessment of hBAL for scavenging nerve agents. They revealed that hBAL has inverted stereoselectivity for the surrogates of nerve agent compared to human cholinesterases. We observed a remarkable flip of the catalytic histidine driven by the chelation of Zn²⁺. Dealkylation of the conjugate, aka aging, was solely observed for paraoxon.

01 Mar 2014·European Journal of Medicinal ChemistryQ1 · MEDICINE

Synthesis and biological evaluation of phosphorylated flavonoids as potent and selective inhibitors of cholesterol esterase

Q1 · MEDICINE

Article

Author: Wang, Bo ; Tang, Jingming ; Wei, Yingling ; Du, Yidan ; Peng, Guoping ; Peng, Ai-Yun ; Ma, Lin

A series of phosphorylated flavonoids were synthesized and investigated in vitro as inhibitors of pancreatic cholesterol esterase (CEase) and acetylcholinesterase (AChE). The results showed that most of the synthesized compounds exhibited nanomolar potency against CEase, much better than the parent flavonoids. Furthermore, these phosphorylated flavonoids demonstrated good to high selectivity for CEase over AChE, which only showed micromolar potency inhibition of AChE. The most selective and potent inhibitor of CEase (3e) had IC₅₀ value of 0.72 nM and 11800-fold selectivity for CEase over AChE. The structure-activity relationships revealed that the free hydroxyl group at position 5 and phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of CEase. The inhibition mechanism and kinetic characterization studies indicated that they are irreversible competitive inhibitors of CEase.

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