Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Org Biomol Chem. 2011 Jul 7;9(13):4959-76. doi: 10.1039/c1ob05058c. Epub 2011 May 20.
Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(III) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the β-amino alcohols with the hypervalent iodine reagent C(6)F(5)I(OCOCF(3))(2), the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN(3) and the bridged ether synthesis with HBr-AcOH as the key reactions. All the synthesized compounds were evaluated by in vitro MTT assay for cytotoxic activity against the human colon cancer cell line HCT-116. Furthermore, the discorhabdin A oxa analogues were also evaluated against four kinds of tumor model cells, a human colon cancer cell line (WiDr), a human prostate cancer cell line (DU-145) and murine leukemia cell lines (P388 and L1210). For the identification of the target, discorhabdin A and the discorhabdin A oxa analogue were evaluated by an HCC panel assay. In the test, discorhabdins could have a novel mode of action with the tumor cells.
已经合成了各种海洋生物碱 discorhabdins 的类似物。该策略包括使用苯碘（III）双（三氟乙酸盐）（PIFA）进行螺环化、使用高价碘试剂 C（6）F（5）I（OCOCF（3））（2）对β-氨基醇进行氧化断裂、在催化量的 NaN（3）存在下脱甲氧基和脱氢反应以及在 Bridged Ether 合成中使用 HBr-AcOH 作为关键反应。所有合成的化合物均通过体外 MTT 测定法评估对人结肠癌细胞系 HCT-116 的细胞毒性活性。此外，还评估了 discorhabdin A 氧类似物对四种肿瘤模型细胞的活性，包括人结肠癌细胞系（WiDr）、人前列腺癌细胞系（DU-145）和鼠白血病细胞系（P388 和 L1210）。为了确定靶标，通过 HCC 面板测定法评估了 discorhabdin A 和 discorhabdin A 氧类似物。在该测试中，discorhabdins 可能与肿瘤细胞具有一种新的作用模式。
