Bioinformatically design of potential cyclooxygenase-۱ (Cox-۱) inhibitors

Backgrounds: Cyclooxygenase is a key enzyme in the conversion of arachidonic acid toprostaglandins. It is found in many cells in the body, such as white blood cells, the immunesystem, stomach, kidneys, and brain cells. Cyclooxygenase-۱ is mainly produced in noninflammatorycells such as stomach cells and its production is a continuous process. The Cox-۱gene has ۲۲ kb, ۱۱ exons, and lacks TATA-box. Numerous studies revealed serious side effectsby using enzyme inhibitors of Cox-۱. In this research, to decrease the side effects and enhancetheir efficiency, a novel in silico-based inhibitor was designed.Materials and Methods: First, ۲۰۰۰۰ compounds similar in structure of aspirin inhibitor wereextracted from the ZINC database with the files related to the structure of Cox-۱ from RCSB(Research Collaboratory for Structural Bioinformatics). After ligands preparation, all compoundswere docked to Cox-۱ for the selection of ۱۰ potent inhibitors.Results: ۱۰ inhibitors were selected based on Gibbs free energy (least ΔG). According to thedocking findings, inhibitors bound to Cox-۱ lead to conformational changes in enzyme, potentialenergy reduction, and enhancing the inhibitor-enzyme stability.Conclusion: Based on the findings, the inhibitors can decrease the inflammation and pain invarious inflammatory diseases, by insertion to the active site on the basis of more specificity andconsequently less toxicity.

Keywords:

Cyclooxygenase-۱ , Docking , Prostaglandins , Gibbs free energy , Aspirin