Guo Lei, Tsang Siu Wai, Zhang Tong-Xin, Liu Kang-Lun, Guan Yi-Fu, Wang Bo, Sun Han-Dong, Zhang Hong-Jie, Wong Man Shing
Department of Chemistry and Institute of Advanced Materials, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR China; School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. China.
School of Chinese Medicine, Hong Kong Baptist University , Kowloon Tong, Hong Kong SAR China.
ACS Med Chem Lett. 2017 Feb 28;8(3):372-376. doi: 10.1021/acsmedchemlett.7b00033. eCollection 2017 Mar 9.
Accumulating evidence indicates that natural -kaurane diterpenoids show great potential for medical treatment of different pathological conditions including cytotoxicity, antibacterial, and anti-inflammatory activity. Among a variety of diterpenoids tested, (-)-pseudoirroratin A displayed a promising antitumor property and . However, this diterpenoid could merely be isolated in a limited amount from a rare source of . To overcome such scanty source, we developed a novel, facile, and efficient semisynthetic strategy to prepare (-)-pseudoirroratin A from natural (-)-flexicaulin A, which can be expediently obtained from in a great quantity. The three-dimensional structure and the absolute configuration of our synthetic diterpenoid have been determined and confirmed with the X-ray crystallographic analysis. More importantly, we demonstrated for the first time that pseudoirroratin A exerted significant cytotoxicity against human colorectal carcinoma cells via an induction of apoptosis, as well as a remarkable suppression on tumor growth in a colon cancer xenograft mouse model.
越来越多的证据表明，天然贝壳杉烷二萜类化合物在治疗包括细胞毒性、抗菌和抗炎活性在内的不同病理状况方面显示出巨大潜力。在测试的多种二萜类化合物中，(-)-假鸢尾亭A表现出有前景的抗肿瘤特性。然而，这种二萜类化合物只能从稀有来源中以有限的量分离得到。为了克服来源稀少的问题，我们开发了一种新颖、简便且高效的半合成策略，以天然的(-)-柔垂红杉醇A为原料制备(-)-假鸢尾亭A，(-)-柔垂红杉醇A可以方便地大量从[具体来源]获得。我们合成的二萜类化合物的三维结构和绝对构型已通过X射线晶体学分析确定并得到证实。更重要的是，我们首次证明假鸢尾亭A通过诱导凋亡对人结肠癌细胞具有显著的细胞毒性，并且在结肠癌异种移植小鼠模型中对肿瘤生长有显著抑制作用。
