Articles Accepted

The serious GIT side effects of NSAIDs due to their carboxylic acid groups aroused the attention of researchers to manipulate such problem. Conjugates with NSAIDs is a fruitful way for both augmenting the anti-inflammatory activities and reducing side effects. Natural or synthetic coumarins are interesting motifs for anti-inflammatory activity. The scope from this work was to conjugate NSAIDs (Ibuprofen, Diclofenac, Mefenamic acid, Ketorolac, and Indomethacin) with various substituted coumarins through an ester or amide linkages using a virtual screening molecular docking study to investigate their ant-inflammatory activities. COX-1, COX-2, Phospholipase A2, and Carbonic anhydrase were used to investigate the anti-inflammatory activities. Results showed that twenty compounds (out of seventy-five) to be considered as having such effects with scores more than those of the standard inhibitors. These compounds display talented docking connections with the active site in each enzyme with different anti-inflammatory mechanisms. The estimation of their pharmacokinetic performance and their drug-likeness according to the ADME study were encouraging in terms of GI absorption, circulation bioavailability and overall drug-likeness, so there is a good chance for these compounds to be established as real drugs.