Hyperelodiones A-C, monoterpenoid polyprenylated acylphoroglucinols from Hypericum elodeoides, induce cancer cells apoptosis by targeting RXRα
| Autor: | Junjie Chen, Ting Lin, Daren Qiu, Yujie Huang, Fu-Rong Yu, Wen-Jing Tian, Guanghui Wang, Rong Ding, Cuiling Sun, Mi Zhou, Hai-Feng Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Circular dichroism Stereochemistry Phytochemicals Molecular Conformation Apoptosis Plant Science Horticulture 01 natural sciences Biochemistry Hypericum elodeoides HeLa Transactivation chemistry.chemical_compound Structure-Activity Relationship Tumor Cells Cultured Humans Molecular Biology Taxonomy Cell Proliferation chemistry.chemical_classification Retinoid X Receptor alpha biology Dose-Response Relationship Drug 010405 organic chemistry Chemistry General Medicine Biodiversity biology.organism_classification Antineoplastic Agents Phytogenic 0104 chemical sciences Molecular Docking Simulation Cancer cell MCF-7 Cells Monoterpenes Drug Screening Assays Antitumor Lead compound Hypericum 010606 plant biology & botany Tricyclic HeLa Cells |
| Zdroj: | Phytochemistry. 170 |
| ISSN: | 1873-3700 |
| Popis: | 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 RXRα-LBD, whereas hyperelodione C showed the strongest interaction with a KD of 12.81 μΜ. In addition, hyperelodiones A-C dose-dependently inhibited RXRα 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 RXRα-LBD and induce HeLa and MCF-7 cell apoptosis. |
| Databáze: | OpenAIRE |
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