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首页> 外文期刊>The Journal of Organic Chemistry >Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole A possessing picomolar human solid tumor cell growth inhibitory activity
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Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole A possessing picomolar human solid tumor cell growth inhibitory activity

机译:佛波唑同系物的合成和生物学评价,导致发现和制备规模的合成具有皮摩尔人实体瘤细胞生长抑制活性的(+)-氯佛波唑A

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摘要

Highly convergent syntheses of eight phorboxazole congeners and their evaluation against a diverse panel of human solid tumor cancer cell lines have been achieved. Specifically, the C(45-46) alkyne, alkene, and alkane phorboxazole A analogues [(+)-4-(+)-6] were constructed and found to display single digit nanomolar cell growth inhibitory activities in a series of human cancer cell lines. The structurally simplified C(11-15)-acetal congener (+)-20Z also proved potent albeit reduced (cf. 34.6 nM) when evaluated against the same cell line panel. Importantly, (+)-C(46)-chlorophorboxazole A (3) displayed picomolar (pM) inhibitory activity in several cell lines.
机译:已经实现了八种邻苯二唑同源物的高度融合合成,并针对多种人类实体瘤癌细胞系进行了评估。具体来说,C(45-46)炔烃,烯烃和烷烃phorboxazole A类似物[(+)-4-(+)-6]被构建并发现在一系列人类癌症中显示出一位数的纳摩尔细胞生长抑制活性。细胞系。经结构简化的C(11-15)-乙缩醛同源物(+)-20Z,即使针对同一细胞系评估,其效价也有所降低(约34.6 nM)。重要的是,(+)-C(46)-氯代荧光唑A(3)在几种细胞系中均表现出皮摩尔(pM)抑制活性。

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