Coixol,
a derivative of 2-benzoxazolinone extracted from coix (Coix
lachryma-jobi L. var. ma-yuen 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 (9c) or nitrofuran (9j) moieties displayed
more pronounced activity than coixol and celecoxib. Mechanistic investigations
revealed that 9c and 9j 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.
In
vivo studies confirmed the anti-inflammatory
activity of 9c and 9j in a xylene-induced
mice auricles edema model. The preliminary in
vitro and in
vivo research
findings suggest that 9c and 9j have the
potential to be developed as anti-inflammatory agents.
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