Chrysosporazines A–E: P-Glycoprotein Inhibitory Piperazines from an Australian Marine Fish Gastrointestinal Tract-Derived Fungus, Chrysosporium sp. CMB-F214

Chemical analysis of Chrysosporium sp. CMB-F214, yielded five new piperazines, chrysosporazines A–E ( 1 – 5 ), with structures assigned by spectroscopic and X-ray analyses and biosynthetic considerations. The chrysosporazines 2 – 5 exist as an equilibrium of major and minor N -acyl rotamers, while 1 – 3 incorporate an unprecedented hexahydro-6 H -pyrazino[1,2- b ]isoquinolin-6-one scaffold. The noncytotoxic chrysosporazines reverse doxorubicin drug resistance in P-glycoprotein overexpressing colon carcinoma cells (SW620 Ad300), with 2 delivering a comparable gain in sensitivity to the positive control, verapamil.