Li Dong-Dong, Dai Lin-Lin, Zhang Na, Tao Zun-Wei
Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China.
Tianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China.
Bioorg Med Chem Lett. 2015 Oct 1;25(19):4092-6. doi: 10.1016/j.bmcl.2015.08.035. Epub 2015 Aug 18.
A series of novel nitrogen mustard sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. Of the newly synthesized compounds, compound 6 exhibited a potent effect against hepatocellular carcinoma in vitro and in vivo. SAR analysis indicated that introduction of a nitrogen mustard group to the structure of sophoridinic acid significantly enhance the antitumor activity. Moreover, molecular docking study exhibited benzyl group introduced to the nitrogen atom at the 12-position and aryl nitrogen mustard group at the 4'-carboxyl region for compound 6 were beneficial for the higher anticancer activity. This work provides useful information for further structural modifications of these compounds and for the synthesis of new, potent antitumor agents.
设计、合成了一系列新型氮芥槐定酸衍生物，并对其细胞毒性进行了评估。在新合成的化合物中，化合物6在体外和体内均对肝细胞癌表现出显著效果。构效关系分析表明，在槐定酸结构中引入氮芥基团可显著增强其抗肿瘤活性。此外，分子对接研究显示，化合物6在12位氮原子上引入苄基以及在4'-羧基区域引入芳基氮芥基团有利于提高抗癌活性。这项工作为这些化合物的进一步结构修饰以及新型高效抗肿瘤药物的合成提供了有用信息。
