Harringtonine (HT) is a naturally occurring alkaloid isolated from the plant genus Cephalotaxus. It possesses antileukemic activity and has been clinically utilized for the treatment of acute leukemia and lymphoma. Sodium periodate (NaIO₄) was reacted with HT to produce five HT derivatives including four novel compounds. Their antiproliferative activity against HL-60 acute promyelocytic leukemia cells revealed that the presence of the C-5′ methyl group enhances the antiproliferative activity because the IC₅₀ values of the HT derivatives, including HT1 (5′-de-O-methylharringtonine), were at least 2000 times higher (>100 μM) than that of HT (∼47 nM). In addition, an indirect competitive enzyme-linked immunosorbent assay (icELISA) using a monoclonal antibody against HT (mAb 1D2) revealed that these antiproliferative activities were related to their cellular uptake. These results indicated that esterification of HT1 at the C-4′ carboxylic acid group may enhance the antiproliferative activity of HT.

中文翻译：

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高碘酸钠介导的Harringtonine衍生物及其对HL-60急性白血病细胞的抗增殖活性

Harringtonine（HT）是从植物头孢属中分离的天然生物碱。它具有抗白血病的活性，已在临床上用于治疗急性白血病和淋巴瘤。高碘酸钠（NaIO ₄）与HT反应生成5种HT衍生物，其中包括4种新化合物。它们对HL-60急性早幼粒细胞白血病细胞的抗增殖活性表明C-5'甲基的存在增强了抗增殖活性，因为HT衍生物（包括HT1（5'-de- O）的IC ₅₀值-甲基harringtonine）（至少> 100μM）比HT（〜47 nM）高至少2000倍。此外，使用抗HT单克隆抗体（mAb 1D2）的间接竞争酶联免疫吸附测定（icELISA）显示，这些抗增殖活性与其细胞摄取有关。这些结果表明HT1在C-4'羧酸基团上的酯化可以增强HT的抗增殖活性。