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

D. Gouiffes, M. Juge, N. Grimaud, L. Welin, M. P. Sauviat, Y. Barbin, D. Laurent, C. Roussakis, J. P. Henichart and J. F. Verbist. Bistramide A, a new toxin from the urochordata Lissoclinum bistratum Sluiter: isolation and preliminary characterization. Toxicon 26, 1129–1136, 1988.—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 (C 40H 68N 2O 8) 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 × 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 ( ic 50 = 4.5 × 10 −8 M ) and P 388 ( ic 50 = 2.0 × 10 −8 M ) and on normal endothelial cells ( ic 50 = 2.2 × 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.