AI Article Synopsis
- * Derivatives 9a and 22c showed strong anti-inflammatory effects with low toxicity, indicated by IC values of 7.7 μM and 5.3 μM, respectively.
- * Further analysis revealed that compound 9a works by reducing phosphorylation of STAT3, which could inhibit IL-17A production and prevent Th17 cell differentiation, suggesting potential for treatment of T cell-related diseases.
Article Abstract
Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential 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 IC values of 7.7 μM and 5.3 μM 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.
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| http://dx.doi.org/10.1016/j.bmc.2022.116936 | DOI Listing |
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