Antitrypanosomal activities of acetylated bruceines A and C; a structure–activity relationship study

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• 作者：Ahmed Elkhateeb (1) (3)
  Yusuke Tosa (1)
  Hideyuki Matsuura (2)
  Kensuke Nabeta (2)
  Ken Katakura (1)
  
• 关键词：Brucea javanica ; Simaroubaceae ; Quassinoids ; Antitrypanosomal activity ; Trypanosoma evansi
• 刊名：Journal of Natural Medicines
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：66
• 期：1
• 页码：233-240
• 全文大小：268KB
• 参考文献：1. Luckins AG (1998) / Trypanosoma evansi in Asia. Parasitol Today 4:137-42 CrossRef
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  7. Hitotsuyanagi Y, Kim IH, Hasuda T, Yamauchi Y, Takeya K (2006) A structure–activity relationship study of brusatol, an antitumor quassinoid. Tetrahedron 62:4262-271 CrossRef
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• 作者单位：Ahmed Elkhateeb (1) (3)
  Yusuke Tosa (1)
  Hideyuki Matsuura (2)
  Kensuke Nabeta (2)
  Ken Katakura (1)
  
  1. Laboratory of Parasitology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan
  3. Phytochemistry and Plant Systematic Department, National Research Centre, Dokki, Giza, Egypt
  2. Laboratory of Bioorganic Chemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, 060-8589, Japan
  
• ISSN：1861-0293

文摘

The crude extract of Brucea javanica showed strong in vitro inhibitory activity against Trypanosoma evansi. Among the isolated quassinoids, bruceines A, C, and bruceantinol were found to be the most potent compounds against T. evansi. To gain a deeper understanding of the relationship between the free hydroxyl groups and the activity, several O-acetylated derivatives of bruceines A and C were synthesized and their in vitro antitrypanosomal activities against trypomastigotes of T. evansi were examined and compared with those of the original compounds. The following structure–activity relationships were observed: (1) the free hydroxyl groups at positions C-3, C-11, and C-12 are essential for antitrypanosomal activity; (2) the C-11 and C-12 hydroxyl groups are more important for the activity than the enolic hydroxyl group at C-3, and; (3) the free hydroxyl group at C-4-of bruceine C does not have any significant effect on the activity.