Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation, a phenomenon termed as “austerity”. Search for the new agents that eliminate the tolerance of cancer cells to nutrition starvation is a promising strategy in anticancer drug discovery. In this study, two new meroterpenoids named callistrilones O and P (1 and 2) together with eight known triterpenes (3–10) were isolated from the active dichloromethane extract of Callistemon citrinus leaves. The structure elucidation of the new compounds was achieved by HRFABMS, 1D, 2D NMR, and ECD quantum calculations. All isolated compounds were tested for their preferential cytotoxicity against PANC-1 human pancreatic cancer cells. Among these, callistrilone O (1) exhibited the most potent preferential cytotoxicity with a PC₅₀ value of 0.3 nM, the strongest activity with over 2000 times potent than the positive control arctigenin. Callistrilone O (1) induced dramatic alterations in PANC-1 cell morphology leading to cell death under nutrient-deprived conditions. Compound 1 also inhibited PANC-1 cell migration and -PANC-1 colony formation under the nutrient-rich condition.

人类胰腺癌对几乎所有常规化疗药物均具有耐药性。众所周知，它通过表现出对营养饥饿的显着耐受性，在血管不足的肿瘤微环境中积极增殖，这种现象被称为“紧缩”。寻找消除癌细胞对营养饥饿的耐受性的新药物是抗癌药物发现中一个有前景的策略。在这项研究中，从Callistemon citrinus叶的活性二氯甲烷提取物中分离出两种新的类萜，名为 Callistrilones O 和 P（ 1和2 ）以及八种已知的三萜（ 3 – 10 ）。通过 HRFABMS、1D、2D NMR 和 ECD 量子计算实现了新化合物的结构解析。测试了所有分离的化合物对 PANC-1 人胰腺癌细胞的优先细胞毒性。其中，callistrilone O( 1 )表现出最有效的优先细胞毒性，PC ₅₀值为0.3nM，活性最强，比阳性对照牛蒡甙元强2000倍以上。 Callistrilone O ( 1 ) 诱导 PANC-1 细胞形态发生显着改变，导致细胞在营养匮乏的条件下死亡。化合物1还在营养丰富的条件下抑制PANC-1细胞迁移和-PANC-1集落形成。