A STUDY OF β-SITOSTEROL, STIGMASTEROL AND 2- HYDROXYHEXADECANOIC ACID METHYL ESTER AGAINST CYCLOXYGENASES (COX-1 & COX-2) AND 5-LIPOXYGENASE AS POTENTIAL PAIN INHIBITORS USING IN-SILICO APPROACH

Background Stylochiton lancifolius has been traditionally used for pain and inflammation. Its methanolic extract also showed significant analgesic and anti-inflammatory effects in rats. This study aims to investigate the molecular interactions of its bioactive compounds, characterized as β-sitosterol, stigmasterol, and 2-hydroxy hexadecanoic acid methyl ester with Cyclooxygenases (COX-1 & COX-2) and 5-Lipoxygenase (5-LOX) using molecular docking. Results The compounds obey Lipinski’s rule of five and showed relatively low acute organ toxicity. All the compounds showed low affinity to COX-1 and COX-2 receptors with no important interaction with the receptors’ active site. But β-sitosterol and stigmasterol have high affinity to 5-LOX; β-sitosterol formed an interaction with His372 while stigmasterol formed bonds with His372 and Arg596 in the receptor’s active site. Conclusion Our study demonstrated that compounds have acceptable oral bioavailability properties and low acute organ toxicity profile. They have low affinity for COX-1 and COX-2 receptors with low levels of interaction. Conversely, β-sitosterol and stigmasterol have high affinity to 5-LOX and show important interaction with this receptor. Therefore, they are better inhibitors of 5-LOX so they should be further optimized for 5-LOX activity.