Identification of potential anti-inflammatory bioactive compounds from Withania somnifera (L.) Dunal: Molecular docking studies using Glide

Non-steroidal anti-inflammatory drugs and COX-2 inhibitors bind to COX-2 and provide relief from the symptoms of pain and inflammation. However, they lack anti-thrombotic activity and hence lead to cardiovascular and renal liabilities apart from gastrointestinal irritation. J Martel-Pelletier et al. reported that dual 5-LOX/COX inhibitors are potential new drugs to treat inflammation. They act by blocking the formation of both prostaglandins and leucotrienes but do not affect lipoxin formation. Such combined inhibition avoids some of the disadvantages of selective COX-2 inhibitors and spares the gastrointestinal mucosa. The search can be focused on plant natural products that may offer treatment for inflammation than currently used drugs. As an attempt to identify such natural alternates with anti-inflammatory activity, a set of 57 compounds from Withania somnifera, were docked against homology modeled human 5-LOX/COX-2 enzymes using GLIDE 5.0. Among the compounds analysed, five alkaloids, namely, Withasomine (Glide score of –7.96 for COX-2 and –5.05 for 5-LOX); Cuseohygrine (Glide score of –6.75 for COX-2 and –6.16 for 5-LOX); anahygrine (Glide score of –6.72 for COX-2 and –5.81 for 5-LOX); 3-tropyltigloate (Glide score of –6.08 for COX-2 and –4.14 for 5-LOX) and tropine (Glide score of –5.71 for COX-2 and –4.48 for 5-LOX) were identified as potent and selective inhibitors of 5-LOX/COX-2 compared to currently available drug molecules. Rofecoxib, Celecoxib, Lumiracoxib and Valdecoxib showed inhibitory activity only for COX-2 (Glide score was –6.92, -5.54, 5.75, and -6.44) and not with LOX-5. These alkaloids from W. somnifera are potential lead compound for developing new anti-inflammatory drug.