新型熊果酸衍生物与查耳酮缀合物的合成及其抗肿瘤活性初步评价

Synthesis and preliminary anti-tumor activity of novel ursolic acid derivative-chalcone conjugates

摘要: 以天然产物熊果酸为先导化合物，将查耳酮通过酯化反应拼接到熊果酸衍生物得到10个熊果酸衍生物-查耳酮缀合物，其结构均通过¹H NMR，¹³C NMR和HRMS加以确认。初步的生物活性结果表明，这些缀合物对CNE2、KB、MCF-7、A549和HepG2细胞均有抑制活性。特别是对MCF-7细胞的抑制活性强于熊果酸和临床上应用的药物他莫昔芬，其中化合物 11e (IC₅₀=4.7 μmol/L)的抗乳腺癌活性最强，是他莫昔芬(IC₅₀=15.2 μmol/L)的近3倍；同时，这些缀合物对正常的MCF-10A和VERO细胞没有毒性，安全性较他莫昔芬高。

Abstract: Ten novel conjugates with ursolic acid core and different chalcone ligands were synthesized via esterification using the natural ursolic acid as starting material. The structures of these conjugates were confirmed by ¹H NMR, ¹³C NMR and HRMS. The preliminary biological results showed that these compounds displayed significant antiproliferative effect on CNE2, KB, MCF-7, A549 and HepG2 cells. These compounds were more effective than ursolic acid and tamoxifen against MCF-7 cells. Especifically, compound 11e (IC₅₀=4. 7 μmol/L)showed the greatest potency against MCF-7, which was about 3-times more potent than tamosifen(IC₅₀=15. 2 μmol/L). Additionally, all conjugates were nontoxic to health MCF-10A and VERO cells, and had higher security than tamoxifen.