熊果酸与白藜芦醇缀合物的合成及其抗肿瘤活性评价

目的 设计、合成熊果酸与白藜芦醇缀合物，并对其抗肿瘤活性进行研究。方法 以熊果酸为原料，通过酯化反应合成了熊果酸-白藜芦醇缀合物，并采用MTT法评价缀合物的体外抗肿瘤活性。结果 合成了12个熊果酸-白藜芦醇缀合物，其结构经¹H-NMR和MS进行确证。初步的生物活性结果表明，目标缀合物对乳腺癌细胞MCF-7和MDA-MB-231均有抑制活性，其中缀合物13b-c和15b-c对MCF-7的抑制活性强于熊果酸、白藜芦醇及阳性药物他莫昔芬。此外，目标缀合物对正常的MCF-10A细胞没有毒性。结论 熊果酸结构中引入白藜芦醇结构单元可提高其抗肿瘤活性。

Synthesis and Preliminary Anti-tumor Activity Evaluation of Ursolic Acid-resveratrol Conjugates

OBJECTIVE To design and synthesize ursolic acid-resveratrol conjugates and investigate their anti-cancer activities. METHODS Ursolic acid-resveratrol conjugates were synthesized from ursolic acid by esterification reaction, and the in vitro antitumor activity of target conjugates was assessed by MTT assay. RESULTS Twelve ursolic acid-resveratrol conjugates were synthesized, and structures were characterized by ¹H-NMR and MS analysis. The preliminary biological results showed that these conjugates displayed inhibitory activity on both MCF-7 and MDA-MB-231. Specifically, the inhibitory activity of conjugate 13b-c and 15b-c on MCF-7 was stronger than that of ursolic acid, resveratrol and the positive drug of tamoxifen. Additionally, all conjugates were nontoxic to normal MCF-10A cells. CONCLUSION The introduction of resveratrol unit into the structure of ursolic acid can enhance its anti-tumor activity.