State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
Bioorg Med Chem Lett. 2021 Jul 1;43:128066. doi: 10.1016/j.bmcl.2021.128066. Epub 2021 Apr 26.
In order to discover potential antitumor agents from natural products, chemical modifications of ergostane-type triterpenoids from Antrodia camphorata yielded ten new compounds. They include nine C-26 amide derivatives of antcin G (1) and a methyl antcin B (4) derivative with hydroxyamino groups at C-3 and C-7. Chemical structures of the new compounds were elucidated by NMR and MS analyses. Furthermore, cytotoxicities of the triterpenoid derivatives were evaluated using four human cancer cell lines (HL60, U251, SW480, and MCF-7). As a result, 1a, 1g, and 4a exhibited potent cytotoxic activities against HL60, U251, and SW480 with IC values of 0.7 ± 0.9, 2.9 ± 1.3, and 2.2 ± 0.6 μM, respectively. Molecular docking indicates that 1a, 1g, and 4a have strong binding affinity with DNA topoisomerase IIα (-9.3, -7.9, and -7.4 kcal/mol, respectively), and that they could be potent topoisomerase IIα inhibitors.
为了从天然产物中发现潜在的抗肿瘤药物，我们对樟芝中的麦角甾烷型三萜进行了化学修饰，得到了 10 个新化合物。它们包括 9 个安特灵 G（1）的 C-26 酰胺衍生物和一个 C-3 和 C-7 位带有羟氨基的甲基安特灵 B（4）衍生物。新化合物的化学结构通过 NMR 和 MS 分析得到阐明。此外，还使用四种人癌细胞系（HL60、U251、SW480 和 MCF-7）评估了三萜衍生物的细胞毒性。结果表明，1a、1g 和 4a 对 HL60、U251 和 SW480 具有很强的细胞毒性，IC 值分别为 0.7±0.9、2.9±1.3 和 2.2±0.6 μM。分子对接表明，1a、1g 和 4a 与 DNA 拓扑异构酶 IIα 具有很强的结合亲和力（分别为-9.3、-7.9 和-7.4 kcal/mol），它们可能是有效的拓扑异构酶 IIα 抑制剂。
