Abstract
Inducible cyclooxygenase-2 (COX-2) is a crucial enzyme involved in the processes of inflammation and carcinogenesis, primarily by catalyzing the production of prostaglandin E2 (PGE2), a significant mediator of inflammation. In this study, we designed and synthesized a series of novel chrysin derivatives to evaluate their anti-inflammatory potential through COX-2 inhibition using in vitro cultures of RAW264.7 macrophages and in silico molecular docking assays. Among the synthesized derivatives, compounds 1a and 8 demonstrated significant inhibition of lipopolysaccharide (LPS)-stimulated proinflammatory cytokine production, including interleukin-6 and tumor necrosis factor-alpha, in RAW264.7 cells. Additionally, these derivatives effectively inhibited PGE2 secretion through COX-2 enzyme inhibition in LPS-stimulated RAW264.7 cells. Molecular docking simulation results revealed that 1a and 8 possess high binding affinities for the COX-2 active site, indicating a strong potential for enzyme inhibition. Furthermore, druglikeness and ADMET predictions for these compounds indicated favorable pharmacokinetic properties, suggesting their suitability as drug candidates. Therefore, compounds 1a and 8 hold promise as potential anti-inflammatory agents for further development.