由于丹皮酚存在水溶性差、易升华和稳定性较差等缺点,其生物利用度较低,制约了丹皮酚在肿瘤治疗方面的应用和疗效.为了提高丹皮酚的生物活性,对丹皮酚结构进行了修饰改造.以丹皮酚为原料,利用不同的连接桥,设计合成了 4种新型的双丹皮酚衍生物(1a～1d),其结构经1H NMR、13 C NMR以及HR-MS(ESI)表征.采用CCK-8法测试了所有化合物对小鼠乳腺癌(4T1),小鼠黑色素瘤(B16),人宫颈癌(Hela),人黑色素瘤(A375)和人肺癌(A549)5种细胞株的增殖抑制活性.结果表明:所合成的化合物均具有一定的抗肿瘤活性,其中化合物1b表现出显著的效果,优于丹皮酚,特别是对4T1(IC50=8.70 μM)和B16(IC50=9.77 μM)细胞株的毒性较强.设计出的新型丹皮酚前药衍生物具有较好的抗肿瘤活性,值得进一步研究.
Synthesis and In Vitro Anticancer Evaluation of Novel Dipaeonol Derivatives
Paeonol has the disadvantages of poor water solubility,easy volatilization and poor stability,which leads to its low bioavailability and restricts its application and efficacy in the treatment of tumors.In order to improve the activityty of paeonol,the structure of paeonol was modified.Four di-paeonol derivatives(1a～1d)were designed and synthesized by using paeonol as the starting material and diaminoalkyl compounds as the connecting bridge.The structures of the target compounds were confirmed by 1H NMR,13 C NMR and HR-MS(ESI).The in vitro cytotoxicity of all target compounds against cell lines(4T1,B16,Hela,A375,A549)was examined by CCK-8 assay.The results showed that all the target compounds had certain antitumor activities,among which compound 1b showed sig-nificant effect,especially on 4T1(IC50=8.70 μM)and B16(IC50=9.77 μM)are more toxic.The designed novel dipaeonol derivatives have better antitumor effects and deserve further investigation.
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