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Synthesis and anti-proliferative activity of allogibberic acid derivatives containing 1,2,3-triazole pharmacophore
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2018-05-18 , DOI: 10.1016/j.bmcl.2018.05.038
Ming-Jiang Wu , Dong-Mei Wu , Jing-Bo Chen , Jing-Feng Zhao , Liang Gong , Ya-Xiao Gong , Yan Li , Xiao-Dong Yang , Hongbin Zhang

Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,β-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC50 values of 0.25–1.72 µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.



中文翻译:

含1,2,3-三唑药效基团的脲醛酸衍生物的合成及抗增殖活性

设计并合成了60种含有1,2,3-三唑药效基团的新脲醛酸衍生物。关键的化学过程包括赤霉素中A环的芳构化,同化别的叠氮化物的形成以及铜与炔烃介导的惠斯根1,3-偶极环加成反应。许多含有α,β-不饱和酮部分的杂种表现出优异的体外细胞毒性活性。一些杂种对MCF-7和SW480细胞系的选择性更高,其IC 50值至少比顺铂(DDP)高8倍。对于所有测试的五种肿瘤细胞系,最有效的化合物C43C45比顺铂(DDP)具有更强的细胞毒性,IC 50值为0.25–1.72 µM。作用机理的研究表明,变质三唑衍生物C45可以诱导SMMC-7721细胞株的S期细胞周期阻滞和凋亡。

更新日期:2018-05-18
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