Magnorolins A–L: sesquiterpenoids with diverse skeletons from the fruits of Magnolia grandiflora and their cytotoxic and anti-inflammatory activities

Abstract

Phytochemical investigation on the fruits of Magnolia grandiflora L. (Magnoliaceae) led to the isolation and characterization of sixteen sesquiterpenoids, including twelve previously undescribed sesquiterpenoids with diverse carbon skeletons, magnorolins A–L (1–3, 5–12, and 15), and four known analogues. Their structures were established by detailed spectroscopic methods, NMR, HR-ESI-MS, ECD calculations, and single-crystal X-ray diffraction analysis. Notably, compound 1 represents an unprecedented C17-germacrene-type sesquiterpenoid bearing a 1,7-dioxaspiro[4.4]nonane moiety; compounds 5 and 6 are rare C18-guaiane-type sesquiterpenoids; and compounds 8 and 9 are unusual guaiane-type sesquiterpenoids characterized by an oxygen bridge between C-6 and C-10. The isolated compounds were evaluated for biological activity in vitro, revealing that 3, 4, 13, 14, and 16 exhibited potent cytotoxic activities against five human cancer cell lines (K562, A549, HepG2, MDA-MB-231, and SW480) with IC₅₀ values ranging from 6.07 to 31.15 µM. Furthermore, compounds 3, 4, 13, and 16 showed strong inhibitory effects on lipopolysaccharide-induced nitric oxide release in RAW 264.7 macrophages, with IC₅₀ values of 14.46 ± 0.12, 6.74 ± 0.05, 6.03 ± 0.09, and 12.20 ± 0.13 µM, respectively. This study enriches the structural diversity of sesquiterpenoids from M. grandiflora and provides valuable experimental basis for the further development and utilization of this plant in innovative drug discovery.