Hyperelodiones A-C, monoterpenoid polyprenylated acylphoroglucinols from Hypericum elodeoides, induce cancer cells apoptosis by targeting RXRα
Hyperelodiones A-C, monoterpenoid polyprenylated acylphoroglucinols from Hypericum elodeoides, induce cancer cells apoptosis by targeting RXRα
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DOI：
10.1016/j.phytochem.2019.112216
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发表时间：
2020-02-01
期刊：
影响因子：
3.8
通讯作者：
Chen, Haifeng
中科院分区：
文献类型：
--
作者：
Qiu, Daren;Zhou, Mi;Chen, Haifeng
Hyperelodione A-C是从金丝桃中分离得到的3个未见文献报道的具有6/6/6稠合三环核的单萜多异戊二烯化酰基间苯三酚。通过HRESIMS和NMR数据确定了它们的结构。通过电子圆二色光谱的计算和比较，结合它们共同的生物合成来源，确定了强碘二酮A-C的绝对构型。荧光猝灭试验表明，hyperelodione A-C可以与RXR α-LBD结合，而hyperelodione C显示出最强的相互作用，K-D为12.81 μ M。此外，hyperelodiones A-C剂量依赖性地抑制HeLa和MCF-7细胞的RXR α反式激活和生长。其中，hyperelodione C表现出最强的抑制活性和剂量依赖性PARP裂解。分子对接结果表明，超碘二酮C与超碘二酮A和超碘二酮B的作用模式不同。因此，hyperelodione C可以被认为是用于癌症治疗的有希望的先导化合物，其可以结合RXR alpha-LBD并诱导HeLa和MCF-7细胞凋亡。
Hyperelodiones A-C, three undescribed monoterpenoid polyprenylated acylphloroglucinols possessing 6/6/6 fused tricyclic core, were isolated from Hypericum elodeoides Choisy. Their gross structures were elucidated by HRESIMS and NMR data. The absolute configurations of hyperelodiones A-C were assigned by their calculated and compared electronic circular dichroism (ECD) spectra combined with their common biosynthetic origin. A fluorescence quenching assay suggested that hyperelodiones A-C could bind to RXR alpha-LBD, whereas hyperelodione C showed the strongest interaction with a K-D of 12.81 mu M. In addition, hyperelodiones A-C dose-dependently inhibited RXR alpha transactivation and the growth of HeLa and MCF-7 cells. Among them, hyperelodione C showed the most potent inhibitory activities and dose-dependent PARP cleavage. Molecular docking results suggested that hyperelodione C showed a different interaction mode compared with hyperelodione A and hyperelodione B. Thus, hyperelodione C can be considered as a promising lead compound for cancer therapy, which can bind to RXR alpha-LBD and induce HeLa and MCF-7 cell apoptosis.