Unveiling the anti-inflammatory potential of organoselenium Schiff bases: computational and in vitro studies

Novel organoselenium (OSe) Schiff bases (3a-c and 5a-c) were designed and synthesized by a simple and convenient approach to obtain good to excellent yields (up to 87%). Their chemical structures were confirmed by different spectroscopic and spectrometric techniques (FT-IR, NMR, and MS). The anti-inflammatory potential of the synthesized OSe Schiff bases (3a-c and 5a-c) was assessed by the protein expression analysis of inflammation-related genes. Interestingly, the anti-inflammatory activity of OSe Schiff bases 3a-c and 5a-c was confirmed by the produced downregulation of the inflammatory proteins (COX-2, IL-6, and IL-1 beta) by (0.43, 0.52, 0.49, and 0.36), (0.65, 0.54, 0.66, and 0.50), and (0.50, 0.44, 0.56, and 0.50)-fold-change, respectively. Furthermore, the binding affinities of the newly designed candidates were examined against the COX-2 receptor using a molecular docking approach. The compounds showed promising binding scores and exhibited similar binding modes as the co-crystallized inhibitor of COX-2 as confirmed through 200 ns molecular dynamic (MD) simulations and MM-GBSA calculations. The DFT study analyzed the electronic properties of compounds 3a-c and 5a-c, revealing that compound 3c exhibited the lowest energy gap and highest stability, while compound 5a demonstrated the greatest electron affinity. Notably, this study showed that the synthesized OSe Schiff bases 3a-c and 5a displayed a significant anti-inflammatory activity, highlighting their potential in biomedical applications.