Molecular docking study of hydroxyquinolone derivatives as COX enzyme inhibitors

Cyclooxygenases (COXs) are essential enzymes involved in the biosynthesis of prostanoids, which play key roles in inflammation and various physiological processes. COX-1 is responsible for maintaining normal homeostatic functions, whereas COX-2 is inducible and primarily expressed during inflammatory and pathological conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibiting COX enzymes; however, their non-selective action often leads to adverse effects, prompting the development of selective COX-2 inhibitors.

Heterocyclic compounds, particularly hydroxyquinolin-2-ones, have attracted significant attention due to their diverse pharmacological activities, including antibacterial, anticancer, and anti-inflammatory properties. In this study, we focused on designing and evaluating in silico of hydroxyquinolin-2-one derivatives as potential therapeutic agents targeting inflammation and infectious diseases.

Molecular docking studies were carried out on the synthesized hydroxyquinolin-2-one derivatives to assess their binding affinity toward the COX enzyme. The results demonstrated promising docking scores for all derivatives, indicating a strong potential for COX inhibition. Compounds with the highest docking scores formed significant interactions with key residues in the COX active site, primarily through hydrogen bonding and other stabilizing interactions. These interactions were facilitated by the presence of carbonyl and hydroxyl groups in the ligand structures, highlighting their crucial role in enhancing binding affinity and stability within the enzyme's active site.