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含二苯甲酮类化合物的抗胰腺癌细胞增殖活性筛选

Benzophenones from with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line.

机构信息

Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

出版信息

J Nat Prod. 2021 May 28;84(5):1607-1616. doi: 10.1021/acs.jnatprod.1c00150. Epub 2021 May 19.

Abstract

The antiausterity strategy is a promising approach for the discovery of lead compounds with unprecedented anticancer activities by targeting the tolerance of cancer cells to nutrition starvation. These agents are selectively cytotoxic under the tumor microenvironment-mimicking condition of nutrition starvation, without apparent toxicity in the normal nutrient-rich condition. In this study, an ethanol extract of showed antiausterity activity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC value of 13.2 μg/mL. Phytochemical investigation of this active extract led to the isolation of eight benzophenones (-), including six new compounds, named betuphenones A-F (-), and three known xanthones (-). The structure elucidation of the new compounds was achieved by HRFABMS, NMR, and ECD spectroscopic analyses. A plausible biogenetic pathway of the new compounds was proposed. Compounds - displayed antiausterity activity with PC values of 4.9-8.4 μM. Moreover, compounds and induced alterations in PANC-1 cell morphology under nutrient-deprived conditions and also inhibited PANC-1 colony formation under nutrient-rich conditions.

摘要

抗营养匮乏策略是一种很有前途的方法,它可以通过靶向癌细胞对营养饥饿的耐受来发现具有前所未有抗癌活性的先导化合物。这些药物在模拟营养饥饿的肿瘤微环境条件下具有选择性细胞毒性,在正常富含营养的条件下没有明显的毒性。在这项研究中, 显示出在营养缺乏条件下对人胰腺癌细胞 PANC-1 的抗营养匮乏活性,PC 值为 13.2 μg/mL。对这种活性提取物的植物化学研究导致了八种二苯甲酮(-)的分离,包括六个新化合物,命名为 betuphenones A-F(-)和三个已知的黄烷酮(-)。新化合物的结构通过高分辨 FABMS、NMR 和 ECD 光谱分析得到阐明。提出了新化合物的可能生物合成途径。化合物 - 具有抗营养匮乏活性,PC 值为 4.9-8.4 μM。此外,化合物 和 在营养缺乏条件下诱导 PANC-1 细胞形态改变,并在营养丰富条件下抑制 PANC-1 集落形成。

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