Discovery of potent ATP citrate lyase inhibitors from Tripterygium wilfordii Hook. f.: a structural and bioactivity analysis.

Feifei Huang, Dian Liu, Yang Han, Tao Hou, Jixia Wang, Yanfang Liu, Xinmiao Liang, Qing Xu, Yan Li, Boquan Qu, Xiaonian Li, Zhimou Guo, Fengbin Luo, Yunhui Zhu, Jiatao Feng

Journal: Phytochemistry 2025;239():114581

PMID: 40517791

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Abstract

Seven undescribed compounds (1-2, 7, 14 and 25-27), and twenty-three known compounds (3-6, 8-13, 15-24 and 28-30) were isolated using multidimensional preparative chromatography from supercritical fluid extracts of Tripterygium wilfordii Hook. f., comprising two sesquiterpenoid macrolide alkaloids, two diterpenoids, and three triterpenoid compounds. Their structures were elucidated using a comprehensive analysis of NMR spectroscopic data and by comparing the experimental and calculated ECD data. Furthermore, the absolute stereochemistry of compound 2 was unambiguously confirmed by single-crystal X-ray diffraction analysis. The inhibitory activities of the isolated compounds on ATP citrate lyase were systematically evaluated. Compounds 19, 24, 25, 26 and 28 exhibited notable inhibitory effects, with compound 19 displaying an IC value of 0.44 ± 0.04 μM.

Address: Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; University of Chinese Academy of Sciences, Beijing, 100049, China.; Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China.; Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.; Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China.; Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China. Electronic address: [email protected].; Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China. Electronic address: [email protected].

DOI: 10.1016/j.phytochem.2025.114581

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MeSH Terms: Tripterygium, Enzyme Inhibitors, ATP Citrate (pro-S)-Lyase, Molecular Structure, Structure-Activity Relationship, Diterpenes, Crystallography, X-Ray, Molecular Conformation, Triterpenes, Drug Discovery