Investigation of Sapelenins as potential anti-inflammatory compounds through network pharmacology: in silico study

Abstract Inflammation is a fundamental aspect of the body’s innate defense mechanism, leading to several diseases like rheumatoid arthritis and cardiovascular disorders. Cyclooxygenase-2 (COX-2) plays a central part in pain and inflammation modulation. It leads to the formation of pro-inflammatory prostaglandins, which cause pain. This is a very important target for the development of new anti-inflammatory drugs. The nonsteroidal anti-inflammatory drugs (NSAIDs) that are frequently used to treat inflammation have adverse effects, including gastrointestinal and cardiovascular effects. This study aims to investigate the anti-inflammatory potential of fourteen (14) new triterpene derivatives, named Sapelenins (Sapelenins A to N) through in silico analysis, including molecular docking, molecular dynamics, MM-GBSA, DFT, drug-likeness, and pharmacokinetics prediction. Molecular docking and re-scoring were performed to select the best COX-2 inhibitors. Among the 14 Sapelenins compounds, only two (SAP J and SAP N) exhibited better affinity with COX-2 than the co-crystallized ligand. Molecular dynamics indicated the stability of the COX-2-SAP J and COX-2_SAP N complexes. The calculated free binding energy demonstrated strong stability of SAP J (ΔGbind: -72.33 kcal/mol) and SAP 4 (ΔGbind: -53.22 kcal/mol) with COX-2 compared to the co-crystallized ligand (ΔGbind: -46.26 kcal/mol). DFT analysis revealed that SAP J presents a better profile as potential anti-inflammatory. Additionally, SAP J and SAP N displayed acceptable drug-likeness and pharmacokinetic properties. Thus, pending confirmation through in vitro and in vivo tests, SAP J and SAP N can be considered as potential anti-inflammatories, with SAP J proving to be the hit compound..