title: Isolation of 6-deoxytetrodotoxin from the pufferfish, Takifugu pardalis, and a comparison of the effects of the C-6 and C-11 hydroxy groups of tetrodotoxin on its activity.
abstract: Identification of new tetrodotoxin (TTX, 1) analogues would be significant in the elucidation of its biosynthetic pathway and a study of its structure-activity relationships. In this study, a new TTX analogue, 6-deoxyTTX (2), was isolated from the ovary of the pufferfish, Takifugu pardalis, and the structure was determined using spectroscopic methods. Compound 2 was also identified in other marine animals, Nassarius snail and blue-ringed octopuses, using LC-MS. Furthermore, we investigated the voltage-gated sodium channel blocking activity of 2 by examination of the inhibitory activities to cytotoxicity induced by ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a). The activities were then compared with those of 1, 11-deoxyTTX (3), and 6,11-dideoxyTTX (4). The EC50 value for 2 was estimated to be 6.5±2.2 nM, approximately 3-fold larger than that of 1 (2.1±0.6 nM) and approximately 20-fold smaller than that of 3. These results suggested that contribution of the C-6 hydroxy group to the activity is less than that of the C-11 hydroxy group.
authors.affiliation: Graduate School of Agricultural Science, Tohoku University , 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi, 981-8555, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kudo
authors.forename: Julian
authors.initials: J
authors.lastname: Finn
authors.forename: Kohei
authors.initials: K
authors.lastname: Fukushima
authors.forename: Satsuki
authors.initials: S
authors.lastname: Sakugawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Cho
authors.forename: Keiichi
authors.initials: K
authors.lastname: Konoki
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D005260:Female; D051379:Mice; D015394:Molecular Structure; D010042:Ouabain; D013329:Structure-Activity Relationship; D023741:Takifugu; D013779:Tetrodotoxin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014701:Veratridine / Q000378:metabolism
chemical_list: C525987:6,11-dideoxytetrodotoxin; D013779:Tetrodotoxin; D010042:Ouabain; D014701:Veratridine