Discovery of 5-Methylcoumarin Polyketide Derivatives from Gerbera piloselloides Using Feature-Based Molecular
Shi-Lin Chen1,2, Hui-Hui Wang1,2, Rui Yang1,2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, People's Republic of China.
Abstract:
Feature-based molecular networking (FBMN), combined with diagnostic ion analysis, facilitated the identification of bioactive 5-methylcoumarin polyketide derivatives with unique skeletal structures from Gerbera piloselloides. This approach led to the isolation of six pairs of 5-methylcoumarin polyketide derivatives, including five pairs of previously undescribed enantiomers. Their structures and absolute configurations were unequivocally determined using spectroscopic data, calculated and experimental electronic circular dichroism (ECD) data, and X-ray diffraction analysis. Notably, compound 1 features a unique combination of 5-methylcoumarin with mixed phenylpropanoid and acetophenone moieties, whereas 2 represents the first 5-methylcoumarin monoterpene containing a benzofuran lactone ring. An in vitro assay revealed that 1 inhibited nitric oxide production and reduced levels of the pro-inflammatory cytokines TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner.
