Chemical constituents of Callistemon citrinus from Egypt and their antiausterity activity against PANC-1 human pancreatic cancer cell line

Abstract Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. The cell is known for its remarkable tolerance to conditions of starvation “austerity” resulted from the uncontrolled cell growth and proliferation under nutritional stress. Therefore, targeting the agents that can eliminate this tolerance to austere conditions is a promising strategy in anticancer drug discovery. Following this strategy, two new meroterpenoids named callistrilones O and P (1−2) 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. 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 condition. Compound 1 also inhibited PANC-1 cell migration in a quantitative real-time experiment and significantly inhibited PANC-1 colony formation under the nutrient-rich condition.