Zhu Hucheng, Chen Chunmei, Tong Qingyi, Chen Xintao, Yang Jing, Liu Junjun, Sun Bin, Wang Jianping, Yao Guangmin, Luo Zengwei, Xue Yongbo, Zhang Yonghui
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
Sci Rep. 2015 Oct 6;5:14772. doi: 10.1038/srep14772.
Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperisampsins H-M (1-6), were isolated from the aerial parts of Hypericum sampsonii, together with five known analogs (7-11). The structures of 1-6 were established by extensive spectroscopic analyses, including HRESIMS and NMR. In addition, the absolute configurations of these new compounds were determined by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first examples of PPAPs possessing a unique γ-lactone ring at C-23, while 3-6 differed from normal PPAPs with an unprecedented 1,2-dioxane ring. Compounds 1-7 were evaluated for their cytotoxic activities against a panel of human cancer cell lines in vitro, of which 3, 4, and 6 exhibited significant cytotoxic activities with IC50 values ranging from 0.56 to 3.00 μM. Moreover, compound 3 induces leukemia cell apoptotic death, evidenced by activation of caspase-3, degradation of PARP, up-regulation of Bax, and down-regulation of Bcl-2 and Bcl-xl.
从元宝草的地上部分分离出6种新的多环多异戊烯基酰基间苯三酚（PPAPs），命名为金丝桃素H - M（1 - 6），以及5种已知类似物（7 - 11）。通过广泛的光谱分析，包括高分辨电喷雾电离质谱（HRESIMS）和核磁共振（NMR）确定了1 - 6的结构。此外，通过电子圆二色光谱（ECD）计算确定了这些新化合物的绝对构型。化合物1和2是在C - 23位具有独特γ - 内酯环的PPAPs的首个实例，而化合物3 - 6与正常PPAPs不同，具有前所未有的1,2 - 二氧六环环结构。对化合物1 - 7进行了体外针对一组人类癌细胞系的细胞毒性活性评估，其中化合物3、4和6表现出显著的细胞毒性活性，IC50值范围为0.56至3.00 μM。此外，化合物3诱导白血病细胞凋亡死亡，这通过半胱天冬酶 - 3的激活、聚（ADP - 核糖）聚合酶（PARP）的降解、Bax的上调以及Bcl - 2和Bcl - xl的下调得以证明。
