Sesquiterpene lactones from Centipeda minima and their STING inhibitory activities

Five undescribed sesquiterpene lactones, named minimolides M-Q (1-5), along with twelve known analogues (6-17), were isolated from the whole plants of Centipeda minima. The structures of these previously undescribed compounds were elucidated using extensive spectroscopic methods (IR, UV, HRESIMS, and NMR), and the complete structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. Among the isolates, compounds 5, 10, 13, 14, 16, and 17 demonstrated STING inhibitory activity in DMXAA-stimulated RAW264.7-Lucia-ISG cells. Subsequent western blotting and RT-qPCR assays revealed that 5 suppressed DMXAA- and cyclic GMP-AMP (cGAMP)-induced phosphorylation of the STING-TBK1-IRF3/p65 signaling cascade, thereby inhibiting STING-dependent gene expression in murine RAW264.7 macrophages and human THP1-derived macrophages, respectively.