Synthesis of skeletal analogues of saxitoxin derivatives and evaluation of their inhibitory activity on sodium ion channels Na V1.4 and Na V1.5

Ryoko Shinohara, Takafumi Akimoto, Osamu Iwamoto, Takatsugu Hirokawa, Mari Yotsu-Yamashita, Kaoru Yamaoka, Kazuo Nagasawa

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Skeletal analogues of saxitoxin (STX) that possess a fused-type tricyclic ring system, designated FD-STX, were synthesized as candidate sodium ion channel modulators. Three kinds of FD-STX derivatives 4 a-c with different substitution at C13 were synthesized, and their inhibitory activity on sodium ion channels was examined by means of cell-based assay. (-)-FD-STX (4 a) and (-)-FD-dcSTX (4 b), which showed moderate inhibitory activity, were further evaluated by the use of the patch-clamp method in cells that expressed Na V1.4 (a tetrodotoxin-sensitive sodium channel subtype) and Na V1.5 (a tetrodotoxin-resistant sodium channel subtype). These compounds showed moderate inhibitory activity towards Na V1.4, and weaker inhibitory activity towards Na V1.5. Uniquely, however, the inhibition of Na V1.5 by (-)-FD-dcSTX (4 b) was "irreversible".

本文言語English
ページ(範囲)12144-12152
ページ数9
ジャーナルChemistry - A European Journal
17
43
DOI
出版ステータスPublished - 2011 10 17

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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