Yamauchi Satoshi, Wukirsari Tuti, Ochi Yoshiaki, Nishiwaki Hisashi, Nishi Kosuke, Sugahara Takuya, Akiyama Koichi, Kishida Taro
Graduate School of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan; South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan.
Graduate School of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan.
Bioorg Med Chem Lett. 2017 Sep 1;27(17):4199-4203. doi: 10.1016/j.bmcl.2017.06.070. Epub 2017 Jun 27.
The new lignano-9,9'-lactones (α,β-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC=12μM), however, it was inactive against HeLa cells (EC>100μM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC values of 10μM and 9.4μM against HL-60 cells, respectively. Against HeLa cells, the EC value of the derivative 66 was 27μM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference.
合成了新型里格纳诺-9,9'-内酯（α,β-二苄基-γ-丁内酯木脂素），其细胞毒性高于牛蒡子苷元。著名的具有细胞毒性的牛蒡子苷元对HL-60细胞显示出活性（EC = 12μM），然而，它对HeLa细胞无活性（EC>100μM）。具有里格纳诺-9,9'-内酯结构的合成的（3,4-二氯，2'-丁氧基）衍生物55和（3,4-二氯，4'-丁基）衍生物66对HL-60细胞的EC值分别为10μM和9.4μM。对于HeLa细胞，衍生物66的EC值为27μM。通过将活性与相应的9,9'-环氧结构（四氢呋喃化合物）进行比较，表明了55和66的内酯结构对于更高活性的重要性。里格纳诺-9,9'-内酯芳香环上的取代基影响细胞毒性水平，观察到超过10倍的差异。
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