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

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 stigmasterol, β-sitosterol and 2-hydroxy hexadecanoic acid methyl ester against 5-Lipoxygenase (5-LOX), cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) enzymes using molecular docking.

The compounds have good bioavailability and minimal acute organ toxicity. All the compounds had minimal activity on cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) receptors, exhibiting no significant 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.

Our study demonstrated that compounds have acceptable oral bioavailability properties and low acute organ toxicity profile They exhibit low activity on for both cyclooxygenase receptors and have minimal levels 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.