Interaction of acetaminophen and caffeine towards cyclooxygenase-2 (COX-2) in inhibition of prostaglandin (PGH 2 ) synthesis

Abstract

Pain is a response of inflammation and can lead to several problems such as morbidity. Inflammation mediated by prostaglandin, which is produced by arachidonic acid and catalyzed by cyclooxygenase. Cyclooxygenase which is responsible for inflammation is COX-2. Acetaminophen can inhibit prostaglandin synthesis through COX-2 and caffeine known as an adjuvant. Analysis of interaction was done by in silico. Ligands, acetaminophen (CID1983) and caffeine (CID2519), was prepared by Discovery Studio v.16 and PyRx then reacted toward COX-2 (1CVU) using PatchDock. Interaction of protein and ligands and energy binding analysed by Discovery Studio v.16 and PatchDock respectively. Energy binding of caffeine towards COX-2 acetaminophen complex is the highest and COX-2 with acetaminophen is the lowest. Interestingly, acetaminophen bind to COX-2 active site, although with the lowest energy and its position is shifted by caffeine when caffeine binds to COX-2 acetaminophen complex. All ligands bind to COX-2 inhibition sites, Ser 530; Tyr 385; Val 523, resulting inhibition of COX-2. Although caffeine can modulate COX-2 inhibition, the combination of caffeine can lead to several gastrointestinal problems. Inhibition of COX-2 can be done by acetaminophen only and it more harmless, besides acetaminophen can bind towards COX-2 active sites with or without caffeine.