The first dimeric indole-diterpenoids from a marine-derived Penicillium sp. fungus and their potential for anti-obesity drugs

Hui-Fang Du; Lei Li; Ya-Hui Zhang; Xu Wang; Cheng-Yan Zhou; Hua-Jie Zhu; Charles U Pittman; Jia-Wen Shou; Fei Cao

doi:10.1007/s42995-024-00253-x

The first dimeric indole-diterpenoids from a marine-derived Penicillium sp. fungus and their potential for anti-obesity drugs

Mar Life Sci Technol. 2024 Oct 8;7(1):120-131. doi: 10.1007/s42995-024-00253-x. eCollection 2025 Feb.

Authors

Hui-Fang Du¹, Lei Li¹, Ya-Hui Zhang¹, Xu Wang¹, Cheng-Yan Zhou¹, Hua-Jie Zhu², Charles U Pittman³, Jia-Wen Shou⁴, Fei Cao^{1

4}

Affiliations

¹ College of Pharmaceutical Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnostics of Education Ministry of China, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, 071002 China.
² School of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018 China.
³ Department of Chemistry, Mississippi State University, Mississippi State, MS 39762 USA.
⁴ School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.

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.

Keywords: 3T3-L1 cell; Absolute configuration; Dimeric indole-diterpenoid; Marine-derived fungus; Penicillium sp..