Pteryxin - A promising butyrylcholinesterase-inhibiting coumarin derivative from Mutellina purpurea

Pteryxin is a dihydropyranocoumarin derivative found in Apiaceae family. In this study, pteryxin, which was previously isolated from the fruits of Mutellina purpurea, was investigated for its inhibitory potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are the key Enzymes in the pathology of Alzheimer's disease (AD). The compound was tested in vitro using ELISA microplate reader at 100 μg/ml and found to cause 9.30 ± 1.86% and 91.62 ± 1.53% inhibition against AChE and BChE, respectively. According to our results, pteryxin (IC₅₀ = 12.96 ± 0.70 μg/ml) was found to be a more active inhibitor of BChE than galanthamine (IC₅₀ = 22.16 ± 0.91 μg/ml; 81.93± 2.52% of inhibition at 100 μg/ml). Further study on pteryxin using molecular docking experiments revealed different possible binding modes with both polar and hydrophobic interactions inside the binding pocket of BChE. Top docking solution points out to the formation of two hydrogen bonds with the catalytic residues S198 and H438 of BChE as well as a strong π - π stacking with W231. Therefore, pteryxin as a natural coumarin seems to be a strong BChE Inhibitor, which could be considered as a lead compound to develop novel BChE inhibitors for AD treatment.