Discovery of stereospecific cytotoxicity of (8R,8'R)-trans-arctigenin against insect cells and structure-activity relationship on aromatic ring.
Discovery of stereospecific cytotoxicity of (8R,8'R)-trans-arctigenin against insect cells and structure-activity relationship on aromatic ring.
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DOI：
10.1016/j.bmcl.2020.127191
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发表时间：
2020-04
影响因子：
2.7
通讯作者：
S. Yamauchi;Asuka Nishimoto;H. Nishiwaki;K. Nishi;T. Sugahara
中科院分区：
文献类型：
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作者：
S. Yamauchi;Asuka Nishimoto;H. Nishiwaki;K. Nishi;T. Sugahara
牛蒡子苷元的立体异构体之一（8 R，8′R）-trans-form 1对昆虫细胞、Sf 9和NIAS-AeAl-2细胞具有立体特异性的细胞毒作用。通过与其他立体异构体的比较，阐明了8′ R立体化学对高活性的重要性。另一方面，未观察到立体异构体对癌细胞HL-60的活性水平范围更广。使用带有（8 R，8′R）-反式形式的衍生物进行构效关系研究，以显示3-碘代、4-碘代和3，4-亚甲二氧基衍生物28、29和36与（8 R，8′R）-反式牛蒡子苷元1具有相同水平的活性。在硫羰基衍生物的检测中，4-碘硫羰基和3，4-亚甲二氧基硫羰基衍生物66，67显示出与（8 R，8′R）-trans-arctigenin相似的活性水平1。（8 R，8′R）-trans-arctigenin 1可促进Sf 9细胞核糖体28 SrRNA基因的表达，但对DNA无降解作用。
One of the arctigenin stereoisomers, (8R,8′R)-trans-form1, showed stereospecific cytotoxicity against insect cells, Sf9 and NIAS-AeAl-2 cells. By the comparison with other stereoisomers, the most importance of the 8′Rstereochemistry for the higher activities was clarified. On the other hand, the wider range of activity level among stereoisomers against cancer cells, HL-60, was not observed. The structure-activity relationship research using derivatives bearing (8R,8′R)-trans-form was performed to show the same level of activities of 3-iodo, 4-iodo, and 3,4-methylenedioxy derivatives28,29, and36as (8R,8′R)-trans-arctigenin1. In the examination of thiono derivatives, 4-iodo thiono and 3,4-methylenedioxy thiono derivatives66,67showed similar level of activities to that of (8R,8′R)-trans-arctigenin1. The expression of ribosomal 28S rRNA gene of Sf9 cells was increased by (8R,8′R)-trans-arctigenin1, whereas a degradation of DNA was not observed.