Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

Four new sesquiterpene lactones (SLs) ( 1 - 4 ), along with a biosynthetically related SL ( 5 ), have been isolated from the leaves of Magnolia grandiflora . Magrandate A ( 1 ) is notable as the first C18 homogemarane type SL, featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one core. Compounds 2 and 3 , representing the first instances of chlorine -substituted gemarane-type SL analogs in natural products, were also identified. The structures of these isolates were elucidated through a combination of spectroscopic data analysis, electronic circular dichroism calculations, and X-ray single -crystal diffraction analysis. All isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 cells. Notably, 3 - 5 showed a significant inhibitory effect on nitric oxide production, with IC 50 values ranging from 0.79 to 4.73 mu mol<middle dot>L -1 . Additionally, 4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines, with IC 50 values between 3.09 and 11.23 mu mol<middle dot>L -1 .