ポスターセッション

一覧　トップ

分化・アポトーシス誘導活性におけるBrefeldin A の新規ファルマコホアの探索： 朱継文¹、名倉ふみ¹、永沢秀子^1、宇都義浩¹、野尻久雄²、堀　均¹ （¹徳島大・工・生物、²帝京大・薬）

New Pharmacophore Requirements in Brefeldin A for　Differentiation and Apoptosis Inducing Activity: Ji-Wen ZHU¹, Fumi NAGURA¹, Hideko NAGASAWA¹, Yoshihiro UTO¹, Hisao NOJIRI², Hitoshi HORI¹ (¹Dept. Biol. Sci. & Tech., Fac. Engg., Univ. Tokushima, ² Fac. Pharm. Sci.,Teikyo Univ.)

【Purpose】Brefeldin A (BFA) is a natural product possessing differentiation and apoptosis inducing ability on human malignant cell lines. Previously we proposed that the alpha, beta-unsaturated carbonyl moiety and the conformational rigidity of BFA molecule were important for its activity. This time we synthesized and evaluated some new BFA analogs to identify other pharmacophore requirements for the biological activities.【Experiments & Results】 We synthesized unnatural 4-epi-BFA and 12-substituted analogs from BFA in good yields. These compounds were tested on human colonic carcinoma cell line HCT 116 to estimate apoptosis inducing ability judged by morphological changes and DNA ladder. We also analysized the [¹⁴C]serine-labeled gangliosides pattern change in their de novo synthesis treated with 4-epi-BFA. The results suggested that the configuration of 4-hydroxyl group played a crucial role in BFA's activity and was a new pharmacophore requirement for differentiation and apoptosis.