Anticancer Polymers via the Biginelli Reaction
Anticancer Polymers via the Biginelli Reaction
复制标题
通过 Biginelli 反应制备抗癌聚合物
DOI：
10.1021/acsmacrolett.0c00496
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发表时间：
2020-09-15
影响因子：
7.015
通讯作者：
Tao, Lei
中科院分区：
文献类型：
--
作者：
Li, Yongsan;Tan, Tianhao;Tao, Lei
我们开发了一种聚合物药物策略来探索抗癌聚合物。通过Biginelli反应，合成了一系列含有潜在抗癌活性基团的单体。这些单体通过方便的自由基共聚合反应合成了水溶性聚合物。所得聚合物具有生物相容性，可直接用于抑制不同癌细胞的增殖，而不会释放小分子。理论计算表明，聚合物中的Biginelli基团与EG5蛋白有很强的相互作用，EG5蛋白在癌细胞中高度表达，与细胞有丝分裂密切相关。随后的细胞实验证实，筛选出的聚合物能有效地抑制不同癌细胞的有丝分裂。我们通过多组分反应和理论计算相结合的方法来探索功能聚合物，得到了有前景的抗癌聚合物，这可能为功能聚合物的从头设计铺平道路，并在有机、计算和聚合物化学领域具有重要的意义。
We developed a polymer-drug strategy to explore anticancer polymers. A series of monomers containing groups with potential anticancer activity have been facilely prepared through the Biginelli reaction. These monomers were used to produce water-soluble polymers through convenient radical copolymerization. The resulting polymers are biocompatible and can be directly used to suppress proliferation of different cancer cells without the release of small molecules. Theoretical calculations revealed that Biginelli groups in polymers had strong interaction with the Eg5 protein, which is highly expressed in cancer cells and is closely related to cell mitosis. Subsequent cell experiments confirmed that a screened polymer is efficient in inhibiting mitosis in different cancer cells. Our study of exploring functional polymers via the combination of multicomponent reactions and theoretical calculation resulted in promising anticancer polymers, which might pave a path for de novo designing of functional polymers and have important implications in the fields of organic, computational, and polymer chemistry.