Vibsane型二萜类化合物是珊瑚树中特有的一类化学成分，该类化合物结构复杂多样，同时具有显著的抗肿瘤活性，但目前存在靶点不明确、作用机制不深入和构效关系未阐明等问题。在前期研究工作中，项目申请人所在课题组对珊瑚树化学成分进行了较为系统的研究，并对其中的10个vibsane型二萜类化合物进行了初步的活性测试和机制探讨，从中发现耐药突变型的EGFR受体可能是该类化合物发挥抗肿瘤作用的靶点，同时影响其下游的PI3K/AKT和Ras/Raf/ERK通路。本项目拟在此基础上，采用细胞膜色谱法结合液质联用技术，对vibsane型二萜类活性成分进行快速导向分离，以期获得更多和足够量的化合物；对其抗肿瘤活性进行系统评价，阐明构效关系；明确其抑制肿瘤增殖和逆转耐药的机制，并在体内进行验证。项目研究结果拟为vibsane型二萜类活性成分的抗肿瘤作用研究提供理论依据。

Vibsane-type diterpenes with complex structure are regarded as unique natural products occur only in Viburnum awabuki. It has been reported that these compounds exhibit obvious anti-tumor activities, but the undefined drug targets, unclear action mechanisms and unestablished structure-activity relationships should be further elucidated. In our previous studies, 10 vibsane-type diterpenes were isolated from Viburnum awabuki, and preliminary experiences on anti-tumor effect and action mechanism have been investigated. The results showed that the compounds potentially targeted on mutant EGFR receptor and influenced PI3K/Akt and Ras/Raf/ERK pathways. On the basis of the above results, sufficient amount of vibsane-type diterpenes will be rapid isolated by CMC-LC-MS method. Moreover, the anti-tumor activity will be evaluated systematically to clarify the structure-activity relationships and reveal the mechanisms of tumor proliferation inhibition and resistance reversal in vitro and in vivo. This study will provide theoretical foundations for anti-tumor effect of vibsane-type diterpenes.