The synthetic and biological studies of discorhabdins and related compounds
The synthetic and biological studies of discorhabdins and related compounds
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DOI：
10.1039/c1ob05058c
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Kita, Yasuyuki
中科院分区：
文献类型：
--
作者：
Wada, Yasufumi;Harayama, Yu;Kita, Yasuyuki
已经合成了海洋生物碱的各种类似物，不一致生物碱。该策略包括苯碘(III)双(三氟乙酸酯)(PIFA)的螺环反应、高价碘试剂C6F5I(OCOCF3)(2)对b-氨基醇的氧化裂解、吡咯亚氨基醌单元在NaN3催化下的脱甲苯磺酰化和脱氢反应以及以HBr-ACoH为关键反应的桥联乙醚合成。用体外四甲基偶氮唑盐比色法测定了所有化合物对人结肠癌细胞株HCT-116的细胞毒活性。此外，还对四种肿瘤模型细胞，人结肠癌细胞系(WiDR)、人前列腺癌细胞系(DU-145)和小鼠白血病细胞系(P388和L1210)进行了抗肿瘤活性研究。为了确定目标，不一致蛋白A和不一致蛋白A oxa类似物通过肝细胞癌小组分析进行了评估。在测试中，discorhabdins可能与肿瘤细胞有一种新的作用模式。
Various analogues of the marine alkaloids, discorhabdins, have been synthesized. The strategy contains spirocyclization with phenyliodine(III) bis(trifluoroacetate) (PIFA), oxidative fragmentation of the b-amino alcohols with the hypervalent iodine reagent C6F5I(OCOCF3)(2), the detosylation and dehydrogenation reaction of the pyrroloiminoquinone unit in the presence of a catalytic amount of NaN3 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.