Identification of Compounds for Butyrylcholinesterase Inhibition

Li, Shuaizhang; Li, Andrew J.; Travers, Jameson; Xu, Tuan; Sakamuru, Srilatha; Klumpp‐Thomas, Carleen; Huang, Ruili; Xia, Menghang

doi:10.1177/24725552211030897

Cited by 26 publications

(16 citation statements)

References 42 publications

(49 reference statements)

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“…While acetylcholinesterase (AChE) plays the key role in ending cholinergic neurotransmission Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic function like AChE through hydrolyzing ACh [ 43 ]. Thus, cholinesterase inhibitors are useful substances that help to interfere with the break-down of ACh and prolong its action [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Chemical Composition, Biological Activities and In Silico Analysis of Essential Oils of Three Endemic Prangos Species from Turkey

et al. 2022

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In this study, the essential oils (EOs) obtained from three endemic Prangos species from Turkey (P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) were studied for their chemical composition and biological activities. β-Bisabolenal (12.2%) and caryophyllene oxide (7.9%) were the principal components of P. heyniae EO, while P. meliocarpoides EO contained sabinene (16.7%) and p-cymene (13.2%), and P. uechtritzii EO contained p-cymene (24.6%) and caryophyllene oxide (19.6%), as the most abundant components. With regard to their antioxidant activity, all the EOs were found to possess free radical scavenging potential demonstrated in both DPPH and ABTS assays (0.43–1.74 mg TE/g and 24.18–92.99 mg TE/g, respectively). Additionally, while no inhibitory activity was displayed by P. meliocarpoides and P. uechtritzii EOs against both cholinesterases (acetyl- and butyryl-cholinesterases). Moreover, all the EOs were found to act as inhibitors of tyrosinase (46.34–69.56 mg KAE/g). Molecular docking revealed elemol and α-bisabolol to have the most effective binding affinity with tyrosinase and amylase. Altogether, this study unveiled some interesting biological activities of these EOs, especially as natural antioxidants and tyrosinase inhibitors and hence offers stimulating prospects of them in the development of anti-hyperpigmentation topical formulations.

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Section: Resultsmentioning

confidence: 99%

Chemical Composition, Biological Activities and In Silico Analysis of Essential Oils of Three Endemic Prangos Species from Turkey

et al. 2022

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“…It is well-established from crystal studies that Ser203 and His447 are the two major amino acids important for AChE’s catalytic properties. These two are located in the catalytic and oxyanion hole residues, which also include Glu202, Tyr33, and Trp86, located in the choline-binding pocket, and Trp236, Phe338, Phe297, and Phe295, composing the acyl-binding pocket of the enzyme [ 38 , 39 ]. The binding mode of the co-crystallized inhibitor galantamine, as shown in Table 4 , clearly identified these key residues.…”

Section: Resultsmentioning

confidence: 99%

“…In Table 5 , the ADME results of the top-five ligands measured using the SWISS-ADME server are displayed. Luteolin, quercetin, naringenin, rosmarinic acid, and kaempferol have molecular weights of 286.24, 302.24, 272.25, 360.31, and 286.24 g/mol, respectively; the results of these phenolic substances suggested that they could be easily transported, distributed, and absorbed through the biological membranes [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. In addition, luteolin, quercetin, naringenin, rosmarinic acid, and kaempferol were found to have LogP values of 1.73, 1.23, 1.84, 1.52, and 1.58, respectively, which are consistent with Lipinski’s rule of five.…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-Assisted Extraction, LC–MS/MS Analysis, Anticholinesterase, and Antioxidant Activities of Valuable Natural Metabolites from Astragalus armatus Willd.: In Silico Molecular Docking and In Vitro Enzymatic Studies

Lekmine

Bendjedid²,

Benslama

et al. 2022

Antioxidants

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The Astragalus armatus Willd. plant’s phenolic constituent extraction and identification were optimized using the ultrasound-assisted extraction (UAE) method and the LC–MS/MS analysis, respectively. Additionally, cupric reducing antioxidant capacity (CUPRAC), beta carotene, reducing power, DMSO alcalin, silver nanoparticle (SNP)-based method, phenanthroline, and hydroxyl radical tests were utilized to assess the extract’s antioxidant capacity, while the neuroprotective effect was examined in vitro against acetylcholinesterase enzyme. This study accurately estimated the chemical bonding between the identified phenolic molecules derived from LC–MS/MS and the AChE. The extract was found to contain sixteen phenolic substances, and rosmarinic, protocatechuic, and chlorogenic acids, as well as 4-hydroxybenzoic, hyperoside, and hesperidin, were the most abundant substances in the extract. In all antioxidant experiments, the plant extract demonstrated strong antioxidant activity and a significant inhibitory impact against AChE (40.25 ± 1.41 μg/mL). According to molecular docking affinity to the enzyme AChE, the top-five molecules were found to be luteolin, quercetin, naringenin, rosmarinic acid, and kaempferol. Furthermore, these tested polyphenols satisfy the essential requirements for drug-like characteristics and Lipinski’s rule of five. These results highlight the significance of the A. armatus plant in cosmetics, as food additives, and in the pharmaceutical industry due to its rosmarinic and chlorogenic acid content.

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“…Moreover, the findings show AChE inhibition that is comparable to those reported in anchovy protein hydrolysates (10-60% inhibition, at concentrations higher than those used in this study (i.e., 100-400 mg/mL, [46]), or fish protein hydrolysates (10.5 -40.5% inhibition at 20-50 mg/mL [47]). Although several studies have reported the inhibition of BChE by various compounds (e.g., see [48]), studies reporting inhibition of BChE by milk-derived peptides are scant. In our study, β-casomorphin-5 and β-casomorphin-7 at 1 mg/mL inhibited BChE significantly (i.e., 67% and 81%, respectively).…”

Section: In Vitro Cholinesterase Inhibition By β-Casomorphin-5 and β-...mentioning

confidence: 99%

Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease

et al. 2022

Dairy

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The drug-likeness and pharmacokinetic properties of 23 dairy-protein-derived opioid peptides were studied using SwissADME and ADMETlab in silico tools. All the opioid peptides had poor drug-like properties based on violations of Lipinski’s rule-of-five. Moreover, prediction of their pharmacokinetic properties showed that the peptides had poor intestinal absorption and bioavailability. Following this, two well-known opioid peptides (βb-casomorphin-5, βb-casomorphin-7) from A1 bovine milk and caffeine (positive control) were selected for in silico molecular docking and in vitro inhibition study with two cholinesterase enzyme receptors important for the pathogenesis of Alzheimer’s disease. Both peptides showed higher binding free energies and inhibitory activities to butyrylcholinesterase (BChE) than caffeine, but in vitro binding energy values were lower than those from the docking model. Moreover, the two casomorphins had lower inhibitory properties against acetylcholinesterase (AChE) than caffeine, although the docking model predicted the opposite. At 1 mg/mL concentrations, βb-casomorphin-5 and βb-casomorphin-7 showed promising results in inhibiting both cholinesterases (i.e., respectively 34% and 43% inhibition of AChE, and 67% and 81% inhibition of BChE). These dairy-derived opioid peptides have the potential to treat Alzheimer’s disease via cholinesterase inhibition. However, appropriate derivatization may be required to improve their poor predicted intestinal absorption and bioavailability.

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Identification of Compounds for Butyrylcholinesterase Inhibition

Cited by 26 publications

References 42 publications

Chemical Composition, Biological Activities and In Silico Analysis of Essential Oils of Three Endemic Prangos Species from Turkey

Chemical Composition, Biological Activities and In Silico Analysis of Essential Oils of Three Endemic Prangos Species from Turkey

Ultrasound-Assisted Extraction, LC–MS/MS Analysis, Anticholinesterase, and Antioxidant Activities of Valuable Natural Metabolites from Astragalus armatus Willd.: In Silico Molecular Docking and In Vitro Enzymatic Studies

Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease

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