Zhang Hengyuan, Li Fangzheng, Zhu Peiqing, Liu Jie, Yao Hequan, Jiang Jieyun, Ye Wencai, Wu Xiaoming, Xu Jinyi
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
Chem Biol Drug Des. 2015 Oct;86(4):424-31. doi: 10.1111/cbdd.12543. Epub 2015 Mar 6.
A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.
设计、合成了一系列异恶唑和恶二唑取代的23-羟基桦木酸（HBA）衍生物，并对其抗肿瘤活性进行了评估。大多数新合成的化合物表现出比专利化合物23-羟基桦木酸更强的抗增殖活性，尤其是13e和14a对所有测试癌细胞系的活性比23-羟基桦木酸高约四至七倍。此外，在H22肝癌和B16黑色素瘤异种移植小鼠模型中验证了13e和14a的体内抗肿瘤活性。还基于本研究讨论了这些23-羟基桦木酸衍生物的构效关系。
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