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

Abstract

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.

Chemical composition and cholinesterase, tyrosinase, alpha-amylase and alpha-glucosidase inhibitory activity of the essential oil of Salvia tomentosa

“…In a molecular simulation study performed by Hussein et al (2019), it was found that the bicyclic sesquiterpene δ-cadinene, present in the total extract of the Commiphora myrrha (Nees) plant, bound to the human AChE with a very high affinity of -9.2 kcal/mol, and formed hydrophobic contacts with Trp83, Phe330 and His439 residues localized in the catalytic triad of the enzyme (Hussein et al, 2019). In another in silico study, δ-cadinene exhibited a binding affinity of -6.77 kcal/mol to AChE, the target protein of Alzheimer's disease, and formed pi-alkyl bonds with polar aliphatic residues Trp286 and His447, and hydrophobic contacts with hydrophobic residues Tyr124 and Phe295 (da Silva Barbosa et al, 2020).…”

“…However, viridiflorol exhibits a more favorable drug-like profile since it does not exceed the MLOGP > 4.15 limit that is violated by the other four ligands. As a result, the 'hit' ligands δ-cadinene, viridiflorol, γ-muurolene and αcaryophyllene, in general, show good pharmacokinetic activity and low toxicity (da Silva Barbosa et al, 2020;Hussein et al, 2019;Schepetkin et al, 2021). Cytochrome P450 (CYP) inhibition, on the other hand, is a common handicap observed in all ligands, and may have adverse effects on the drug metabolism of the host organism.…”

The antifeedant properties of bio-oil from Cupressus sempervirens against rice weevil (Sitophilus oryzae) compared to that of Myrrh and Frankincense oils

“…Also, it can be utilized as a biological insecticide on date palm aphids (Al-Keridis, 2022). Some other studies have ascertained the potency of myrrh as an antibacterial, antifungal, antiparasitic, and bio-insecticide natural agent (Allam et al, 2001;Sheir et al, 2001;Perveen et al, 2018;Becheker et al, 2022;).The efficiency of myrrh oil may be attributed to its mode of action as Acetyl Choline esterase (AChE) inhibitor as described by (Hussein et al, 2019) who found that the botanical extracts resulted from leaves, bark, and resin of C. myrrha caused inhibition of AChE activity by 17, 26, and 29% for leaves, bark, and resin respectively.…”

Unveiling the Anti-Cholera and Active Diabetic Renoprotective Compounds of Maqian Essential Oil: A Computational and Molecular Dynamics Study

“…Furthermore, a comprehensive evaluation of ADMET indicated that cedrelanol has the capability to traverse the gastrointestinal tract and the blood-brain barrier. In the context of antibacterial activity and its potential to inhibit cholera toxin-induced intestinal hypersecretion, it is worth noting that the sesquiterpene T-cadinol, isolated from the aromatic resin of Commiphora guidottii (Burseraceae), commonly referred to as scented myrrh, has been documented [46]. Cholera infection is sometimes characterized by the presence of severe electrolyte imbalances and acute kidney injury or inflammation.…”