Chapter 14 - Natural products-based antiinflammatory compounds and phospholipase A2: Molecular docking and molecular dynamics simulations

Abstract

The response of vascular tissues to harmful stimuli is inflammation. Inflammation is normally a defense mechanism and deregulated inflammation causes disease like rheumatoid arthritis, autoimmune diseases, pelvic-inflammation disease, atherosclerosis, myocardial, ischemia, and cancer. Chemical mediators control the process of inflammation. Eicosanoids comprising of prostaglandin, prostacyclin, thromboxanes, and leukotrienes play a critical role in every step of the inflammation. The oxygenated fatty acids are metabolized by cyclooxygenases and lipoxygenases from arachidonic acid. The suppressing the conversion of arachidonic acid into proinflammatory eicosanoids was unsuccessful. As an alternative, designing inhibitors of phospholipases A2 (PLA2), the enzyme that catalyzes the hydrolysis of membrane phospholipids into arachidonic acid has become root for antiinflammatory drug design. Although many PLA2 inhibitors have been reported from terrestrial natural products, it was only in mid-1980s. The first marine natural product myeloid was prove to be the PLA2 inhibitor. The chapter details PLA2, its catalytic mechanisms, and the role of natural products as antiinflammatory agents. Molecular docking studies have been extensively used in understanding the binding of many phytoconstituents from terrestrial and marine natural products. In understanding the binding mechanisms of these with active site residues of PLA2 causing inhibition of inflammation. The results are compared with the binding of cocrystal also. Molecular dynamics simulations have been carried out for a marine compound.