Pharmacophore based virtual screening of natural product database to identify potential lead Cyclooxygenase-2 inhibitors (COX-2)

Inflammation is a key factor linked to almost all chronic and degenerative diseases, including arthritis, heart disease, asthma, neurodegeneration, cancer, kidney and bowel diseases. Since ancient time’s natural products such as turmeric, ginger root extract and some of the essential oils have been used to relieve pain. Till today around 135 Indian medicinal plants screened for their activity on the basis of ethanopharmacology on random basis. The active constituents from these plants are also reported to be selective inhibitors of enzymes such as COX-1, COX-2 which is responsible for inflammation. Such natural product scaffolds find applications in the treatment of inflammation and can also be used for the development of new generation anti-inflammatory drugs with low toxicity and higher therapeutic value. In this paper, we report screening of various natural compounds from an in-house developed bioactive database containing around 10 bioactives. As a first step, known crystallized COX-2 inhibitor SC-558 was used to generate pharmacophore, which was used for initially screening of the database. The result set was further filtered using physico-chemical properties similar to that of the known inhibitor SC-558. Our screening approach identified around 347 structurally similar molecules, which were further docked using the GLIDE software module. The docking studies resulted into 15 compounds with comparable docking score with respect to known inhibitor SC-558.Binding interactions were further studied to get insights into binding pattern of these molecules with respect to binding site of COX-2 enzyme.