Computational insight to putative anti-acetylcholinesterase activity of Commiphora myrrha (Nees), Engler, Burseraceae: a lessen of archaeopharmacology from Mesopotamian Medicine I.

Commiphora spp., Burseraceae family and their resinous matter, myrrh, are used in Mesopotamian medicine as fragrance or antiinsectant. Based on in vitro, leaves, bark, and resin methyl alcohol extract of C. myrrha showed similar inhibitory effects of 17.00, 26.00, and 29.33% for acetylcholinesterase (AChE) as compared to eserine, respectively. The ADMET properties and putative anticholinesterase activity of phytochemicals of myrrh were computationally predicted using in silico tools. Phytochemicals of C. myrrha had acceptable binding affinity (BA) towards principal sites of AChE ranging from - 5.8 (m-cresol) to - 10.5 (abietic acid) kcal/mol. In this regard, all terpenoid compounds (25 out of 28) of myrrh were dual inhibitors since they hydrophobically interacted with both catalytic triad and peripheral anionic site (PAS) of AChE while alpha-terpineol, elemol, and eugenol employed hydrogen bonds with AChE. Cuscohygrine as a pyrrolidine alkaloid has been docked with AChE through hydrogen bonds with PAS and through hydrophobic interactions with catalytic triad thereby we initially proposed it as dual inhibitor of AChE. M-cresol as a methylphenol has been loosely docked with AChE via hydrogen bond and would be a hit molecule for further drug synthesis. This study not only confirmed archaeopharmacological applications of myrrh as antiinsectant or nootropics but also offered an array of terpenoid compounds, cuscohygrine, and m-cresol as a good starting point for hit-to-lead-to-drug optimization phase in synthesis of phyto-nootropics and ecofriendly insecticides.