The First Identification of the Novel Tetrodotoxin Analog, 6-Deoxytetrodotoxin, and its Biological Activity

Tetrodotoxin (TTX) specifically blocks the voltage-gated sodium channels. Identification of novel TTX analogs would be significance in prediction of biosynthetic pathway toward TTX and its structure activity relationship study. In this study, a novel TTX analog, 6-deoxyTTX, was isolated from the ovary of the puffer fish, Fugu pardalis, and the structure was determined using spectroscopic methods. Furthermore, 6-deoxyTTX was identified in the several marine organisms using LC/MS. The inhibitory activities of TTX, 6-deoxyTTX and 11-deoxyTTX to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a) were examined. Their activities and the structure activity relationship on C-6 and C-11 hydroxyl groups of TTX will be discussed.