SuFEx クリック・ケミストリー 末期の薬物機能化
Zilei Liu1,2, Jie Li1,2, Suhua Li2
1Department of Molecular Medicine, The Scripps Research Institute , La Jolla, California 92037, United States.
Journal of the American Chemical Society
|February 17, 2018
まとめ
硫黄 (VI) フッ化物交換 (SuFEx) クリック化学は,新しい抗がん薬候補の迅速な合成を可能にします. この新しい方法では アリルフッ素硫酸塩を素早く生成し 検査することで がん細胞に対する効能を高める化合物が 検出されます
科学分野:
- 薬剤化学
- 有機化学
- 薬物の発見
背景:
- 硫黄 (VI) フッ化物交換 (SuFEx) は,新しいクリック化学技術である.
- SuFEx化学は,新しい化合物を合成するための多用途のプラットフォームを提供します.
- 薬の発見における応用は 未知の領域です
研究 の 目的:
- 96wellプレートにおけるSuFEx化学の in situ方法の開発と検証
- アリルフッ素硫酸ドリバティブの迅速な合成と生物学的スクリーニングを可能にします.
- 抗癌薬の末期機能化におけるSuFExの可能性を調査する.
主な方法:
- フェノルをアリルフッロースルファートに変換する in situ SuFEx反応を開発した.
- 生物学的活動の迅速な評価のために自動合成とスクリーニングを活用した.
- 既知の抗がん剤の 末期機能化を行いました
主要な成果:
- 抗がん細胞増殖活性が向上した3つのアリルフッ素硫酸を特定した.
- フルベストラント・フッ素酸塩系は,ER+乳がん細胞に活性化を示した.
- コンブレタスタチンA4フルオロスルファート系は,薬剤耐性結腸がん細胞に対する効能が70倍に増加した.
結論:
- 現場で開発されたSuFEx方法は,自動合成とスクリーニングと互換性があります.
- このアプローチにより,治療効果が向上した新薬候補の発見が容易になります.
- SuFExの化学は 薬の発見と開発を加速させるのに 重要な可能性を秘めています
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