Interactions of Orthosiphon Stamineus Compounds Against Cox-2 as an Anti-Inflammatory Using in Silico Methods and Toxicity Prediction

Abstract

Objective: Orthosiphon stamineus, or cat's whiskers, are known to have several pharmacological activities, one of which is anti-inflammatory. An in silico study was conducted to determine the active compound with anti-inflammatory activity from Orthosiphon stamineus leaves while also assessing their toxicity. Methods: AutoDock 4 was used to perform molecular docking, while LigandScout 4.4.3 Advanced was used to screen pharmacophores. The Swiss ADME and PreAdmet websites were used to screen the prediction of Lipinski’s rules of 5 and toxicity. Results: In this in silico study on the COX-2 enzyme (PDB ID: 3ln1) with a RMSD validation value of 1.00 Å, Tetramethyl Luteolin emerged as the most promising candidate, exhibiting the lowest binding energy of-9.90 kcal/mol and a KI value of 55.80 nM, indicating favorable interactions within the active site. The compound also satisfied the Lipinski Rules and demonstrated favorable absorption and distribution characteristics, with HIA at 98.440681% and CaCO2 permeability at 53.1689 nm/sec, along with a small BBB value of 0.0154021 and quite good %PPB of 87.388706. Furthermore, Tetramethyl Luteolin obtained a pharmacophore fit score of 32.42, indicating possession of key structural features essential for desired biological activity. Conclusion: The flavonoid-derived compounds in cat's whisker leaf extract show promise as potential anti-inflammatory drug candidates, with Tetramethyl luteolin emerging as the best candidate among nine compounds, meeting Lipinski rules and exhibiting superior ADMET properties. These results highlight the potential of Tetramethyl Luteolin as a lead compound, necessitating additional research into its intended target or biological function.