Abstract
Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20-C-22' linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1-3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-024-00253-x.