Teaching and Research Division, School of Chinese Medicine , Hong Kong Baptist University , 7 Baptist University Road , Kowloon Tong , Hong Kong SAR , People's Republic of China.
Department of Applied Biology and Chemical Technology , The Hong Kong Polytechnic University , Hung Hom , Hong Kong SAR , People's Republic of China.
J Med Chem. 2019 Feb 14;62(3):1541-1561. doi: 10.1021/acs.jmedchem.8b01742. Epub 2019 Jan 25.
Our earliest phytochemical separation of Miliusa sinensis aided us in the isolation of a class of unique miliusanes, which were demonstrated as anticancer lead molecules. In the present study, we isolated 19 miliusanes (1-19), including 11 novel ones (5 and 10-19) from another Miliusa plant ( M. balansae), and synthesized additional derivatives to elucidate the structure-activity relationship of miliusanes. When extrapolated to various carcinoma xenograft mouse models, miliusol (1) and its derivatives 20, 26, and 27 (7.5-40 mg/kg) were demonstrated with tumor inhibitory efficacy comparable or even superior to the mainstay chemotherapeutics paclitaxel or fluorouracil. To gain a molecular insight into their anticancer mechanism, 1-3 (GI 0.03-4.79) were administered to a wide spectrum of human cancer cell lines, including those with specific drug resistance. We further revealed that the antiproliferative properties of miliusanes in carcinoma cells were highly associated with the p21-dependent induction of cellular senescence.
我们最早从三叶海棠中进行的植物化学分离，帮助我们分离出一类独特的三叶海棠烷，它们被证明是抗癌的先导分子。在本研究中，我们从另一种三叶海棠（三叶海棠）中分离出 19 种三叶海棠烷（1-19），其中包括 11 种新型三叶海棠烷（5 和 10-19），并合成了其他衍生物来阐明三叶海棠烷的结构-活性关系。当外推到各种癌异种移植小鼠模型时，三叶海棠醇（1）及其衍生物 20、26 和 27（7.5-40mg/kg）表现出与主要化疗药物紫杉醇或氟尿嘧啶相当或甚至更好的肿瘤抑制功效。为了深入了解它们的抗癌机制，1-3（GI 0.03-4.79）被给予广泛的人类癌细胞系，包括那些具有特定耐药性的细胞系。我们进一步揭示，三叶海棠烷在癌细胞中的增殖抑制特性与细胞衰老过程中 p21 依赖性诱导密切相关。
