Docking and Molecular Dynamic Investigations of Phenylspirodrimanes as Cannabinoid Receptor-2 Agonists

Abdelsattar M Omar; Anfal S Aljahdali; Martin K Safo; Gamal A Mohamed; Sabrin R M Ibrahim

doi:10.3390/molecules28010044

Docking and Molecular Dynamic Investigations of Phenylspirodrimanes as Cannabinoid Receptor-2 Agonists

Molecules. 2022 Dec 21;28(1):44. doi: 10.3390/molecules28010044.

Authors

Abdelsattar M Omar^{1

2

3}, Anfal S Aljahdali¹, Martin K Safo^{4

5}, Gamal A Mohamed⁶, Sabrin R M Ibrahim^{7

8}

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
³ Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁴ Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
⁵ Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USA.
⁶ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁷ Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Abstract

Cannabinoid receptor ligands are renowned as being therapeutically crucial for treating diverse health disorders. Phenylspirodrimanes are meroterpenoids with unique and varied structural scaffolds, which are mainly reported from the Stachybotrys genus and display an array of bioactivities. In this work, 114 phenylspirodrimanes reported from Stachybotrys chartarum were screened for their CB2 agonistic potential using docking and molecular dynamic simulation studies. Compound 56 revealed the highest docking score (-11.222 kcal/mol) compared to E3R_6KPF (native agonist, gscore value -12.12 kcal/mol). The molecular docking and molecular simulation results suggest that compound 56 binds to the putative binding site in the CB2 receptor with good affinity involving key interacting amino acid residues similar to that of the native ligands, E3R. The molecular interactions displayed π-π stacking with Phe183 and hydrogen bond interactions with Thr114, Leu182, and Ser285. These findings identified the structural features of these metabolites that might lead to the design of selective novel ligands for CB2 receptors. Additionally, phenylspirodrimanes should be further investigated for their potential as a CB2 ligand.

Keywords: Stachybotrys; cannabinoid receptors; fungi; industrial development; life on land; molecular docking; phenylspirodrimanes.

MeSH terms

Binding Sites
Cannabinoid Receptor Agonists* / chemistry
Cannabinoid Receptor Agonists* / pharmacology
Ligands
Molecular Docking Simulation
Molecular Dynamics Simulation*
Receptor, Cannabinoid, CB2* / metabolism
Terpenes* / chemistry
Terpenes* / pharmacology

Substances

Cannabinoid Receptor Agonists
Ligands
Receptor, Cannabinoid, CB2
Terpenes

Grants and funding

RG-37-166-43/The Deanship of Scientific Research (DSR) at King Abdulaziz University (KAU), Jeddah, Saudi Arabia has funded this project, under grant no. (RG-37-166-43)