Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents.

Coixol, a derivative of 2-benzoxazolinone extracted from coix ( L. var. Stapf), has demonstrated promising anti-inflammatory activity and low cytotoxicity. In this study, 26 coixol derivatives were designed and synthesized by hybridization with cinnamic acid to identify new anti-inflammatory agents. The anti-inflammatory activities of the derivatives were screened using LPS-induced overexpression of nitric oxide (NO) in RAW264.7 macrophages. On the basis of the screening results, compounds containing furan () or nitrofuran () moieties displayed more pronounced activity than coixol and celecoxib. Mechanistic investigations revealed that and suppressed the expression of induced nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, which was associated with the inhibition of the nuclear factor (NF)-κB signaling pathway. studies confirmed the anti-inflammatory activity of and in a xylene-induced mice auricles edema model. The preliminary and research findings suggest that and have the potential to be developed as anti-inflammatory agents.