New callistrilone epimers from Callistemon citrinus and their antiausterity activity against the PANC-1 human pancreatic cancer cell line

Phytochemical investigation of Callistemon citrinus leaves resulted in the isolation of two new structurally unique callistrilone epimers named callistrilone Q (1) and epicallistrilone Q (2). Both epimers were found to exist in the form of equilibrium conformational isomers. The structural elucidation of the new compounds was achieved by HREIMS in addition to extensive 1D and 2D NMR spectroscopic analyses. The absolute configuration was determined using computational ECD and optical rotation calculations. Both isolated compounds displayed unprecedented preferential cytotoxic activities against PANC-1 human pancreatic cancer cells at the nanomolar level. These compounds also were found to inhibit PANC-1 cell migration under normal nutrient-rich conditions. Both compounds downregulated key proteins involved in the PI3K/Akt/mTOR signaling pathway.