Repurposing of Potential Curcumin Derivatives Against Cyclooxygenase‐2 Using In Silico Methods and Its Implications in Neurological Disorders

Cyclooxygenase-2 (COX-2) plays a crucial role in inflammatory responses and has been implicated in neuroinflammatory processes associated with neurological disorders such as Alzheimer's disease. While selective COX-2 inhibitors (coxib class of drugs) have been developed, their use is limited by adverse effects, necessitating the exploration of alternative therapeutic approaches. This study investigates the potential of curcumin derivatives as COX-2 inhibitors and their possible therapeutic applications in neurological disorders. Previous in silico studies show various amino acids interacting with naturally occurring curcumin derivatives. We explored the potential of 2561 curcumin derivatives as COX-2 enzyme inhibitors by examining their binding affinity to the protein. Using molecular docking, we assessed their interactions with two regions of COX-2, identifying five standout compounds with powerful binding affinities. The binding energies of these compounds lie around -10.7 and -10.6 kcal/mol. To better understand how these top candidates behave in a dynamic biological environment, we ran molecular dynamics simulations focusing on their interactions with one part of the enzyme. These simulations revealed that the compounds formed stable complexes with COX-2, maintaining consistent hydrogen bonds and hydrophobic contacts throughout. RMSD and RMSF graphs exhibit greater stability of these compounds as compared to the control molecule. Finally, energy calculations confirmed that these interactions were not only stable but also energetically favorable, suggesting that several curcumin derivatives could be promising COX-2 inhibitors. This study provides valuable insights into the potential of curcumin derivatives as COX-2 inhibitors and their possible therapeutic applications in neurological disorders. The identified compounds warrant further investigation through in vitro and in vivo studies to validate their efficacy and safety as potential alternatives to current selective COX-2 inhibitors in the treatment of neuroinflammatory conditions.