Synthesis and biological properties of actinomycin D chromophoric analogues substituted at the 7-carbon with aziridine and aminopropoxy functions.
Synthesis and biological properties of actinomycin D chromophoric analogues substituted at the 7-carbon with aziridine and aminopropoxy functions.
复制标题
7-碳原子被氮丙啶和氨基丙氧基取代的放线菌素 D 发色类似物的合成和生物学特性。
DOI：
10.1021/jm00392a018
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发表时间：
1987
影响因子：
7.3
通讯作者：
Sengupta,SK
中科院分区：
文献类型：
--
作者：
Sehgal,RK;Almassian,B;Rosenbaum,DP;Zadrozny,R;Sengupta,SK
功能化叠氮嘧啶在许多有机生物分子中的重要性日益增加，这促使我们开发了一种新的叠氮嘧啶取代放线菌素D （AMD）类似物的合成。7-羟基放线菌素D与2-（碘甲基）氮吡啶反应生成所需的7-（2-氮基甲氧基）放线菌素类似物。在尝试开发这种类似物的替代途径时，7-（2-叠氮-3-碘丙氧基）放线菌素被二甲胺-硼烷络合物还原；该反应不生成三元叠氮吡啶；相反，反应产物被发现是线性的7-（2-氨基丙氧基）放线菌素D.小牛胸腺DNA结合与AMD相当，通过紫外可见差异光谱测量，DNA热变性和CD技术检测。在体外实验中发现，这些类似物对人淋巴细胞CCRF-CEM白血病和B16黑色素瘤细胞的细胞毒性约为V4至1/30。
The growing importance of functionalized aziridines in numreous organic biomolecules led us to develop syntheses of novel actinomycin D (AMD) analogues substituted with an aziridine. Reaction of 7-hydroxyactinomycin D with 2-(iodomethyl) aziridine produced the desired 7-(2-aziridinylmethoxy) actinomycin analogue. In an attempt to develop an alternate route to this analogue, 7-(2-azido-3-iodopropoxy) actinomycin was subjected to reduction with dimethylamine-borane complex; the reaction did not produce the three-membered aziridine; instead the reaction product was found to be linear 7-(2-aminopropoxy) actinomycin D. Calf-thymus-DNA binding of these analogues was comparable to that of AMD as examined by UV-visible differencespectral measurements, thermal denaturation of DNA, and CD techniques. The analogues were found to be about V4 to 1/30 as cytotoxic to humanlymphoblastic CCRF-CEM leukemia and B16 melanoma cells in vitro as AMD.