Bistramide A, a new toxin from the urochordata Lissoclinum bistratum Sluiter: isolation and preliminary characterization.

Two cases of human intoxication caused by the lyophilized powder of Lissoclinum bistratum Sluiter, a New Caledonian ascidian, are reported. The symptoms observed were caused by a substance designated bistramide A (C40H68N2O8) of hitherto unknown chemical structure. Preliminary toxicological investigations indicate that bistramide A may effect the central nervous system, leading to paresthesia and loss of muscle tone. A progressive decrease in cardiac rhythm was also observed in animals. Bistramide A (1.4 x 10(-6) M) did not alter the resting potential of frog heart and skeletal muscle but reduced the amplitude and duration of cardiac action potential and prolonged the interval between action potentials. Bistramide A also has a marked cytotoxic effect on cancer cells KB (IC50 = 4.5 x 10(-8) M) and P 388 (IC50 = 2.0 x 10(-8) M) and on normal endothelial cells (IC50 = 2.2 x 10(-8) M). However, it has not been possible to relate the cytotoxic property to the symptoms of intoxication. Bistramide A may originate from the urochordate itself or from symbiotic algae.