Computer-Aided Drug Design of Anti-inflammatory Agents Targeting Microsomal Prostaglandin E2 Synthase-1 (mPGES-1).

Inflammation is a natural process in response to external stimuli associated with organism protection. However, this reaction could be exaggerated, leading to severe damages related to physiopathological processes, such as rheumatoid arthritis, cancer, diabetes, allergies, infections, among others. Inflammation is mainly characterized by pain, increased temperature, flushing, and edema, which can be controlled using anti-inflammatory drugs. In this context, prostaglandin E2 (PGE2) inhibition has been targeted for designing new compounds with anti-inflammatory properties. It is a bioactive lipid overproduced during an inflammatory process, in which its increased production is carried out mainly by COX-1, COX-2, and microsomal prostaglandin E2 synthase-1 (mPGES-1). Recently, studies have demonstrated that mPGES-1 inhibition is a safe strategy to develop anti-inflammatory agents, which could protect against pain, acute inflammation, arthritis, autoimmune diseases, and different types of cancers. To decrease production costs and increase the probability of discovering active substances, computer-aided drug design (CADD) approaches have been increasingly used for designing new inhibitors. Thus, this review will cover all aspects involving high-throughput virtual screening, molecular docking, dynamics, fragment-based drug design, quantitative structure-activity relationship in seeking new promising mPGES-1 inhibitors.