吲哚基嘧啶的合成及其抗肿瘤活性：海洋天然产物meridianin D类似物
Synthesis and antitumor activity of indolylpyrimidines: marine natural product meridianin D analogues.
作者信息
Radwan Mohamed A A, El-Sherbiny Mahmoud
机构信息
Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, Egypt.
出版信息
Bioorg Med Chem. 2007 Feb 1;15(3):1206-11. doi: 10.1016/j.bmc.2006.11.023. Epub 2006 Nov 16.
Marine indole alkaloid meridianin D analogues have been synthesized starting from the appropriate 3-cyanoacetyl indole. A facile two-step conversion of 3-cyanoacetyl indole to the corresponding cyano meridianin D analogue by treatment with dimethylformamide-dimethylacetal and further cyclization of the resulting enaminonitrile with aminoguanidine is described. Then, alkaline hydrolysis of cyano meridianin D afforded the carboxylic acid analogue. The treatment of acid with 75% H(2)SO(4) afforded the desired 6-debromomeridianin D. Simply treatment of cyano meridianin D analogue with hydrazine hydrate afforded the amidrazone analogue. The biological evaluation indicated that cyano analogue showed good cytotoxic activity with IC(50) values of 0.85 and 2.65microg (against MCF7 and HeLa, respectively), but acid and amidrazone analogues showed high cytotoxicity with IC(50) values of 0.75 and 0.25microg, respectively (against MCF7).
海洋吲哚生物碱美登木素 D 类似物已从合适的 3-氰基乙酰吲哚开始合成。描述了通过用二甲基甲酰胺-二甲基乙缩醛处理将 3-氰基乙酰吲哚简便地两步转化为相应的氰基美登木素 D 类似物，并将所得烯胺腈与氨基胍进一步环化。然后，氰基美登木素 D 的碱性水解得到羧酸类似物。用 75% 的 H₂SO₄ 处理该酸得到所需的 6-脱溴美登木素 D。用肼水合物简单处理氰基美登木素 D 类似物得到脒腙类似物。生物学评价表明，氰基类似物显示出良好的细胞毒性活性，IC₅₀ 值分别为 0.85 和 2.65 μg（分别针对 MCF7 和 HeLa），但酸和脒腙类似物显示出高细胞毒性，IC₅₀ 值分别为 0.75 和 0.25 μg（针对 MCF7）。
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