Identification and bioactivity evaluation of miliusanes from Miliusa sinensis

• Published in: Bioorganic chemistry 2023-11, Vol.140, p.106797-106797, Article 106797
• Main Authors: Xie, Wen-Jian, Xu, Xin-Ya, Xia, Yi-Xuan, Shing Lam, Chu, Chen, Tie, Zhi, Yun-Shi, Ming Lee, Kuan, Song, Xun, Deyrup, Stephen T., He, Zhen-Dan, Zhang, Hong-Jie
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Meroterpenoids; Miliusa sinensis; Miliusanes; Plant natural products
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2023.106797

[Display omitted] •12 new miliusanes belonging to two sub-types identified from M. sinensis.•The novel miliusane with a 2, 5-dione quinone group exhibited potent cytotoxicity.•Structure-activity relationship is discussed to enable miliusane lead optimization.•Miliusanes showed dual functions to inhibit cell migration and induce senescence. Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7–14 and 17–20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 μM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.