Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity
Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity
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发现、合成具有抗癌活性的3-羟基氨基末端基团的新型夫西地酸衍生物
DOI：
10.1016/j.ejmech.2018.10.059
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发表时间：
2019-01-15
影响因子：
6.7
通讯作者：
Bi, Yi
中科院分区：
文献类型：
--
作者：
Ni, Jingxuan;Guo, Mengqi;Bi, Yi
合成了一系列新的夫西地酸衍生物，并对它们对Hela、U87、KBV和MKN 45癌细胞系的体外细胞毒性进行了筛选。首先鉴定了具有抗肿瘤活性的所选FA衍生物，包括化合物4，其表现出良好的抗增殖活性，IC 50值在1.26-3.57 μ M的范围内。进一步的研究表明，化合物4通过以1至10 μ M的剂量依赖性方式减少新合成的蛋白质而增加处于Sub-G（0）/G（1）期的细胞的比率，从而诱导Hela细胞经历凋亡。化合物4对Hela细胞的异种移植瘤也显示出良好的体内抗肿瘤活性，并且没有明显的毒性。这项研究突出了在FA的3-OH位置引入中等长度的氨基末端基团以增强其抗肿瘤活性的优势，并表明化合物4为将来设计更有效的衍生物提供了起点。(C)2018 Elsevier Masson SAS。All rights reserved.
A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC50 values in the range of 1.26-3.57 mu M. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G(0)/G(1) phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 mu M. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future. (C) 2018 Elsevier Masson SAS. All rights reserved.