Molecular docking and simulation studies of a novel labdane type- diterpene from Moluccella aucheri Scheen (Syn. Otostegia aucheri) as human- AChE inhibitor

Moluccella aucheri Scheen belongs to Lamiaceae family and is native to Iran and Pakistan. Different chromatographic and spectroscopic analyses of a dichloromethane extract of M. aucheri's aerial parts led to the isolation of five phytochemicals. They include an undescribed labdane type- diterpene; 6ß -acetoxy-9α-hydroxy-7- oxa- labd-13- ene- 15, 16- olide or moluccelactone (1), and four known compounds: stigmasterol and ß-sitosterol (2, 3), 5-hydroxy-7, 4′-dimethoxyflavone (4) and genkwanin (5). Their chemical structures were determined by spectroscopic data. As a best result, these compounds are firstly reported in this genus and plant. The α-glucosidase and acetylcholine esterase (AChE) inhibitory activity of 1 were evaluated by the protein-ligand docking and molecular dynamics studies. Compound 1 exhibited strong binding affinities towards the active site residues of human-AChE (hAChE) enzyme, while it was not potent against α-glucosidase enzyme. In conclusion, compound 1 is suggested as a potential natural inhibitor of hAChE enzyme in vitro and in vivo tests.