Investigating the anti-inflammatory potential of N-amidic acid organoselenium candidates: biological assessments, molecular docking, and molecular dynamics simulations†

Inflammation is a complex process with many contributing factors, and it often causes pain. The pathophysiology of pain involves the release of inflammatory mediators that initiate pain sensation, as well as edema and other inflammation hallmarks. Selenium-containing compounds (OSe) are very promising for developing new medicines because they can treat many different diseases. In this study, we estimated the anti-inflammatory properties of maleanilic and succinanilic acids containing selenium (OSe). These molecules were designed by combining different strategies to enhance their anti-inflammatory properties. Hence, the anti-inflammatory impacts of compounds 8, 9, 10, and 11 were pursued using inflammatory markers COX-2, IL-1β, and IL-6. Notably, it was revealed that compounds 8, 9, 10, and 11 downregulated COX-2, IL-1β, and IL-6 by (2.01, 1.63, 2.26, and 2.05), (1.42, 1.64, 1.93, and 2.59), and (1.67, 2.54, 2.22, and 4.06)-fold changes, respectively. Moreover, molecular docking studies were conducted on compounds 8, 9, 10, and 11 to pursue their binding affinities for the COX-2 enzyme. Notably, very promising binding scores of compounds 8, 9, 10, and 11 towards the binding site of the COX-2 receptor were attained. Additionally, more accurate molecular dynamics simulations were performed for 200 ns for the docked complexes of compounds 8, 9, 10, and 11 to confirm the molecular docking findings, which ignore the protein's flexibility. Therefore, the exact stability of the N-amidic acids OSe compounds 8, 9, 10, and 11 towards the binding pocket of the COX-2 enzyme was examined and explained as well. Also, the MM-GBSA binding energy was calculated for equilibrated MD trajectory, and 200 snapshots were selected with a 50 ps interval for further analysis. Accordingly, the investigated compounds can be treated as prominent lead anti-inflammatory candidates for further optimization.