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

Autor: Luz RLSA; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil., Almeida RBM; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil., Albuquerque MMS; Department of Biology, State University of Feira de Santana, Feira de Santana, Brazil., Cerqueira APM; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil., Tavares JF; Pharmaceutical Technology Laboratory, University of Paraíba, João Pessoa, Brazil., Silva MSD; Pharmaceutical Technology Laboratory, University of Paraíba, João Pessoa, Brazil., Filho RB; Department of Chemistry, State University of North Fluminense Darcy Ribeiro, Rio de Janeiro, Brazil.; Department of Organic Chemistry, Federal Rural University of Rio de Janeiro, Seropédica, Brazil., Dos Santos Junior MC; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil., Branco A; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil., Botura MB; Department of Health, State University of Feira de Santana, Feira de Santana, Brazil.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2023 Apr; Vol. 101 (4), pp. 855-864. Date of Electronic Publication: 2022 Dec 26.
DOI: 10.1111/cbdd.14195
Abstrakt: 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 1 H- 13 C 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.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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