Ocotea daphnifolia: phytochemical investigation, in vitro dual cholinesterase inhibition, and molecular docking studies

Almeida, Raquel Bianca Marchesine de; Conceição, Rodrigo Souza; Silva, Kryzia Santana da; Santos, Manoelito Coelho dos; Branco, Alexsandro; Botura, Mariana Borges

doi:10.1590/s2175-97902020000418310

Cited by 2 publications

(3 citation statements)

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“…The identification of the plant species was carried out by a botanist, and a voucher specimen (HUPES 205862) was deposited at the herbarium of the State University of Feira de Santana, Brazil. The obtaining of the ethyl acetate extract of O. daphnifolia used in this study and verification of its in vitro dual anticholinesterase activity has been previously described (Almeida et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…Mez is an endemic species in the state of Bahia, and little scientific information was provided in the literature. However, we recently published a study about the in vitro dual anticholinesterase activity of the O. daphinifolia crude extracts (Almeida et al, 2021). In addition, this study aimed to perform the bioguided isolation of the active compounds from the O. daphinifolia ethyl acetate extract and to investigate the intermolecular interactions inside the cholinesterase active sites of their isolated compounds ( 1 and 2 , Figure 1a) by molecular docking studies.…”

Section: Introductionmentioning

confidence: 99%

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Two new dilactonized glycerol glycosides of the dual anticholinesterase active extract from Ocotea daphnifolia using bioguided fractionation and molecular docking studies

et al. 2022

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The dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) is considered as an important strategy for the treatment of Alzheimer's disease. In this study, we applied the bioguided fractionations of Ocotea daphinifolia ethyl acetate active extract to furnish a fraction with high inhibitory activity for AChE and BuChE (82% and 92%, respectively). High‐performance liquid chromatography semipreparative purification of this fraction provided two new natural products: 1‐β‐D‐galactopyranosyl‐glycerol‐2,3‐heptanedionate, (1) whose complete chemical structural elucidation was made with spectrometric analysis (MS, 1D, and 2D NMR) and its minor derivative 1‐β‐D‐gulopyranosyl‐glycerol‐2,3‐heptanedionate; (2) which could be characterized by 2D 1H‐13C heteronuclear single‐quantum correlation spectra analysis. Investigation of the intermolecular interactions with cholinesterases was carried out by molecular docking studies, and results suggested that both compounds are capable to interact with the catalytic site of both enzymes. Compounds 1 and 2 interact with residues of catalytic domains and the peripheral anionic binding site of AChE and BuChE. The results are comparable to those achieved with rivastigmine and galantamine. Thus, this study provides evidence for consideration of the glycosylglycerol from O. daphnifolia as new valuable dual cholinesterases inhibitor.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Two new dilactonized glycerol glycosides of the dual anticholinesterase active extract from Ocotea daphnifolia using bioguided fractionation and molecular docking studies

et al. 2022

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“…Computational strategies can identify essential stereo-electronic requirements for inhibition of more than one target simultaneously, using virtual screening for pharmacophore models, evaluation of interactions between molecules and the target active site and finally, molecular docking, which predicts the spatial orientation of an active compound within its binding site [24,25]. A further computational approach, molecular dynamics (MD) simulation, describes the variation in molecular behavior as a function of time, considering the system's flexibility [26,27]. Those strategies combined can lead to more efficient structures and evaluate the potential activity of compounds not yet synthesized, based only on their chemical structure.…”

Section: Introductionmentioning

confidence: 99%

Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach

Barbosa,

do Bomfim,

de Oliveira

et al. 2023

Pharmaceuticals

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Alzheimer’s disease causes chronic neurodegeneration and is the leading cause of dementia in the world. The causes of this disease are not fully understood but seem to involve two essential cerebral pathways: cholinergic and amyloid. The simultaneous inhibition of AChE, BuChE, and BACE-1, essential enzymes involved in those pathways, is a promising therapeutic approach to treat the symptoms and, hopefully, also halt the disease progression. This study sought to identify triple enzymatic inhibitors based on stereo-electronic requirements deduced from molecular modeling of AChE, BuChE, and BACE-1 active sites. A pharmacophore model was built, displaying four hydrophobic centers, three hydrogen bond acceptors, and one positively charged nitrogen, and used to prioritize molecules found in virtual libraries. Compounds showing adequate overlapping rates with the pharmacophore were subjected to molecular docking against the three enzymes and those with an adequate docking score (n = 12) were evaluated for physicochemical and toxicological parameters and commercial availability. The structure exhibiting the greatest inhibitory potential against all three enzymes was subjected to molecular dynamics simulations (100 ns) to assess the stability of the inhibitor-enzyme systems. The results of this in silico approach indicate ZINC1733 can be a potential multi-target inhibitor of AChE, BuChE, and BACE-1, and future enzymatic assays are planned to validate those results.

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Ocotea daphnifolia: phytochemical investigation, in vitro dual cholinesterase inhibition, and molecular docking studies

Cited by 2 publications

References 30 publications

Two new dilactonized glycerol glycosides of the dual anticholinesterase active extract from Ocotea daphnifolia using bioguided fractionation and molecular docking studies

Two new dilactonized glycerol glycosides of the dual anticholinesterase active extract from Ocotea daphnifolia using bioguided fractionation and molecular docking studies

Development of Potential Multi-Target Inhibitors for Human Cholinesterases and Beta-Secretase 1: A Computational Approach

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