In-silico inhibitory Activities of Tribulusamide D Against Cannabinoid Receptor (CB1)

Abstract

<title>Abstract</title> Many women experience the effect of excess endocannabinoid production in the body by noticing some changes such as anxiety, the effect on learning and memory, reproduction and sex, metabolism, growth, and development. Others take cannabinoids as drugs. Cannabinoids are known to have anti-depressant properties but are also inhibitors of sexual urges. Research has shown that cannabinoids reduce dopamine levels, hence the need to inhibit the activities of cannabinoid receptors found all over the body, especially the brain. This research focuses on in-silico inhibition of cannabinoid receptors which serve as a precursor to the metabolism of cannabinoids. A Cannabinoid Receptor (CB1) PDB was downloaded (7V3Z) from https://www.rcsb.org. The protein was prepared, the sitemap identified and the receptor grid generated too. Tribulusamide D (TD) is a natural product isolated from <italic>Tribullus terrestris</italic> and has been confirmed to have anti-inflammatory activities. TD was drawn using the 2-D sketcher and copied to the 3-D workspace of the maestro Schrodinger suite. The native ligand, <bold>2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol</bold> was used as the reference drug (since it acts as an agonist to the receptor) and was prepared using ligprep module. The prepared protein and ligands were docked using the ligand docking module of the Maestro Schrodinger suite. The docking of the ligands with CB1 shows that Tribulusamide D has a better docking score with a higher negative value than the reference drug and hence could enhance sexual urge when the desire is inhibited by excess cannabi. In-vivo and in-vitro research is recommended to confirm the inhibitory activities of Tribulusamide D against CB1 as predicted by this study.