新規な構造を持つアセトゲニン類をリード化合物とする新しいがん細胞認識分子の探索

点击翻译按钮获取中文摘要

Selective discrimination of tumor cells from normal cells has been a central concern in development of potent therapeutic agents for cancer.A number of studies have been directed to seek tumor-specific molecular targets which exist only in tumor cells not in normal cell.Biochemical investigations on antitumor activity of naturally occurring materials with quite high potency may contribute to such a research.Bullatacin(1),a representative of natural products called annonaceae acetogenins with neighboring bistetrahydrofuran,has impressibly potent antitumor activity with ED_<50>=10^<-15> mug/ml for 9PS,1)and was expected to be a suitable lead compound with which biochemical studies may facilitate to search tumor-specific molecular targets.As the first step for such an approach,we studied versatile chiral synthesis of Bullatacin(1)and its enantiomer which is applicable to the synthesis of other members of this group.In a preliminary investigation on its function,it was found that a model compound(2)has cation transport ability selective to potassium cation,as illustrated in Fig 1,although cation binding ability has not yet been correlated to antitumor activity of 1. We expect that biochemical studies with the synthetic as well as radiolabelled compounds would reveal a molecular target of 1.