Unprecedented Monoterpenoid Polyprenylated Acylphloroglucinols with a Rare 6/6/5/4 Tetracyclic Core, Enhanced MCF-7 Cells' Sensitivity to Camptothecin by Inhibiting the DNA Damage Response.
Xiang-Zhong LiuMi ZhouChun-Chun DuHong-Hong ZhuXi LuShou-Lun HeGuang-Hui WangTing LinWen-Jing TianHai-Feng ChenPublished in: Biomedicines (2021)
(±)-Hypersines A-C (1-3), the three pairs of enantiomerically pure monoterpenoid polyprenylated acylphloroglucinols with an unprecedented 6/6/5/4 fused ring system, were isolated from Hypericum elodeoides. Their structures, including absolute configurations, were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction, and quantum chemical calculations. The plausible, biosynthetic pathway of 1-3 was proposed. Moreover, the bioactivity evaluation indicated that 1a might be a novel DNA damage response inhibitor, and could enhance MCF-7 cell sensitivity to the anticancer agent, camptothecin.
Keyphrases
- dna damage response
- breast cancer cells
- induced apoptosis
- molecular dynamics
- dna repair
- high resolution
- cell cycle arrest
- signaling pathway
- single cell
- molecular docking
- density functional theory
- molecular dynamics simulations
- electronic health record
- monte carlo
- big data
- cell death
- stem cells
- endoplasmic reticulum stress
- machine learning
- mass spectrometry
- crystal structure
- data analysis
- computed tomography
- mesenchymal stem cells