ASCT2靶向抑制剂的合成及抗肿瘤活性研究

Study on Synthesis and Antitumor Activity of ASCT2 Targeted Inhibitor

目的合成新型丙氨酸-丝氨酸-半胱氨酸转运体2(ASCT2)靶向抑制剂,考察其与ASCT2蛋白的结合性及其体外抗肿瘤活性。方法通过酮与伯胺结构化学物反应生成目标化合物,采用核磁共振技术表征其结构;使用AutoDock软件计算化合物与ASCT2的对接能量,进行分子对接;采用CCK-8法分析目标化合物的抗肿瘤活性。结果分子对接结果显示合成的目标化合物与ASCT2蛋白具有良好的亲和性,CCK-8结果显示目标化合物对肿瘤细胞具有一定的抑制作用。结论目标化合物具有抗肿瘤作用,并有望成为新型靶向ASCT2抑制剂。

Objective A novel targeted inhibitor of alanine-serine-cysteine transporter 2(ASCT2)was designed andits banding to ASCT2 protein and its anti-tumor activity in vitro were also investigate in this study.Methods A target compound was synthesized by the condensation of primary amine with ketone compound.The target compound was characterized by NMR.AutoDock software was used to calculate the docking energy of the target compound and ASCT2 protein,as well as perform molecular docking.CCK-8 method was applied to evaluate the antitumor activity.Results Molecular docking showed that the target compound had good affinity with ASCT2 protein.CCK-8 test showed a certain growth inhibitory effect on Kelly cell,BE-2C cell,NLF cell,BXPC3 cell,and HCT116 cell.Conclusion The target compound has good antitumor activity and is expected to be a potential ASCT2 targeted inhibitor.