Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, People's Republic of China.
J Nat Prod. 2021 Feb 26;84(2):339-351. doi: 10.1021/acs.jnatprod.0c00986. Epub 2021 Jan 14.
Twelve undescribed jatrophane diterpenoids, euphpepluones A-L (-), together with seven known analogues (-), were isolated from the whole plant of , and their structures were elucidated by spectroscopic studies. The absolute configurations of and were assigned by X-ray crystallographic analysis. All isolates were investigated for their inhibitory effects against the ATR-Chk1 pathway using a Western blotting assay. As a result, , , , , , and were found to suppress the camptothecin (CPT)-induced phosphorylation of Chk1, indicating that these compounds inhibit the activation of the ATR-Chk1 pathway. A preliminary structure-activity relationship (SAR) study of the isolates was conducted. When compound and CPT were combined, apoptosis was induced in A549 cells with PARP cleavage, while there was no apoptotic effect by treatment with CPT or alone. The data obtained indicate that potentiates the chemotherapeutic sensitivity of A549 cells to CPT.
从全株中分离得到 12 个未描述的 Jatrophane 二萜类化合物， euphpepluones A-L(-)，以及 7 个已知类似物(-)，通过光谱研究阐明了它们的结构。通过 X 射线晶体学分析确定了和的绝对构型。所有分离物均通过 Western blotting assay 检测对 ATR-Chk1 途径的抑制作用。结果表明，、、、、、和能抑制喜树碱 (CPT)诱导的 Chk1 磷酸化，表明这些化合物抑制 ATR-Chk1 途径的激活。对分离物进行了初步的构效关系 (SAR) 研究。当化合物和 CPT 联合使用时，A549 细胞中发生了 PARP 切割诱导的细胞凋亡，而单独用 CPT 或处理则没有细胞凋亡作用。获得的数据表明，增强了 A549 细胞对 CPT 的化疗敏感性。
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