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

• Published in: Chemical biology & drug design Vol. 101; no. 4; pp. 855 - 864
• Main Authors: Luz, Rebecca Lustosa Silva de Almeida, Almeida, Raquel B. M., Albuquerque, Mara Márcia Sampaio, Cerqueira, Amanda Ponce Morais, Tavares, Josean Fechine, Silva, Marcelo Sobral da, Filho, Raimundo Braz, Santos Junior, Manoelito C., Branco, Alexsandro, Botura, Mariana B.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.04.2023
• Subjects: 2D NMR; acetylcholinesterase; Acetylcholinesterase - metabolism; Alzheimer Disease; Biochemistry & Molecular Biology; butyrylcholinesterase; Butyrylcholinesterase - chemistry; Chemistry, Medicinal; Cholinesterase Inhibitors - chemistry; Glycerol; glycosylglycerols; lactone; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Molecular Docking Simulation; Ocotea - metabolism; Ocotea daphnifolia; Pharmacology & Pharmacy; Science & Technology; lactone; butyrylcholinesterase; 2D NMR; AFFINITY; GLUCOSYLGLYCEROL; acetylcholinesterase; PLANTS; Ocotea daphnifolia; INHIBITORS; glycosylglycerols
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.14195

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. New compounds were isolated: 1‐(2‐ciclo‐heptan‐di‐yl)‐3‐β‐D‐galactopyranosyl‐glycerol (1) and 1‐(2‐ciclo‐heptan‐di‐yl)‐3‐β‐D‐gulopyranosyl‐glycerol (2). The semipurified fractions of O. daphnifolia showed dual anticholinesterase effect. The compounds isolated presented in silico interactions with AChE and BuChE.