Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities

Nine new ( 1 – 9 ) and four known ( 10 – 13 ) [13]cytochalasins, along with three known 24-oxa[14]cytochalasins ( 14 – 16 ), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the fibrous root of Parasenecio albus . Their structures were elucidated by interpretation of the nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations were assigned by single-crystal X-ray crystallography, modified Mosher′s method, and by analysis of their experimental electronic circular dichroism (ECD) spectra. Compound 6 could induce cell cycle arrest at G2-phase in CT26 and A549 cells, and displayed moderate cytotoxicity against CT26 and A549 cell lines with IC 50 values of 6.03 and 5.04 μM, respectively. Co-treatment of 7 – 9 , 13 and 16 with tumor necrosis factor related apoptosis inducing ligand (TRAIL) could significantly decrease the cell viability of A549, which revealed that cytochalasins could possibly be a new group of TRAIL sensitizers in lung cancer therapy.