Design, synthesis and in vitro biological evaluation of marine phidianidine derivatives as potential anti-inflammatory agents

Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their po-tential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T-cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC50 values of 7.7 mu M and 5.3 mu M for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases.

Automated summary

In this study, a series of phidianidine derivatives were designed and synthesized. Compound 9a and 22c showed excellent anti-inflammatory activity by inhibiting the production of IL-17A, indicating their potential as drug candidates for T cell-mediated diseases.