Synthesis of the dibenzylbutane lignan LCA derivatives and evaluation of their anti-inflammatory activities

Abstract

The roots of Litsea cubeba (Lour.) Pers have been used for the treatment of rheumatism. We previously extracted and isolated the natural product dibenzylbutane lignan LCA with anti-inflammatory activity. In the current study, using LCA as the lead compound, two series of LCA derivatives with an imide structure and butadiene structure were designed and synthesized. Among them, compounds 10c and 16a showed stronger inhibitory effects on LPS-induced NO and ROS production in RAW264.7 cells. Further study showed that compound 16a not only reduced the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1β, but it also significantly reduced the expression of iNOS and COX-2. Preliminary mechanism of action studies suggested that 16a exerts anti-inflammatory effects by inhibiting the NF-κB signaling pathway. Overall, our results suggest that compound 16a may be used as a promising anti-inflammatory drug to enrich the compound library. Further study into compound 16a could provide research ideas and methods for developing anti-inflammatory drugs.