Ionone-Derived Curcumin Analogs as Potent Anti-Inflammatory Agents

A series of [beta] -ionone-derived curcumin analogs (1a - 1j) have been synthesized by condensation of [beta] -ionone with a variety of aldehydes. The synthesized compounds were screened for their in vitro anti-inflammatory activity against lipopolysaccharide (LPS)-induced expression of the pro-inflammatory cytokines tumor necrosis factor- [alpha] (TNF- [alpha]) and interleukin-6 (IL-6). Five active compounds exhibited dose-dependent inhibition of the release of TNF-[alpha] and IL-6. The active analogs represent a new class of anti-inflammatory agents with improved potency as compared to curcumin. Furthermore, the active compound 1e showed a protective effect against LPS-induced septic mortality in vivo. Our results suggest that the obtained analogs may be further developed as potential agents for the prevention and treatment of inflammatory diseases.