苯丁酸氮芥协同四价铂药物的合成与抗癌活性研究  

Synthesis and Anti-cancer Activity of Platinum(Ⅳ) Drug Modified by Chlorambucil

作　　者：屠思嘉 李泽宁 吕鹤 陈超 TU Sijia;LI Zening;LYU He;CHEN Chao(School of Life Sciences,Huzhou University,Huzhou 313000,China)

机构地区：[1]湖州师范学院生命科学学院,浙江湖州313000

出　　处：《湖州师范学院学报》2021年第2期43-48,共6页Journal of Huzhou University

基　　金：浙江省自然科学基金项目(LQ14B02003);浙江省大学生科技创新活动计划暨新苗人才计划项目(2019R431029);国家级大学生创新创业训练计划项目(202010347045)。

摘　　要：通过酯化反应,在二氯二羟基二氨合铂(Ⅳ)的轴向基团上引入苯丁酸氮芥,合成苯丁酸氮芥协同的四价铂药物,并通过核磁共振和质谱对该化合物进行表征.在体外细胞毒性实验中,二氯二苯丁酸氮芥二氨合铂(Ⅳ)在测试的癌细胞系中(肠癌细胞LoVo、胃癌细胞7901、肺癌细胞A549)均显示出较高的活性.特别是在耐顺铂的A549-R肺癌细胞中,二氯二苯丁酸氮芥二氨合铂(Ⅳ)的半抑制浓度(IC_(50)值)为1.33±0.09μM,药效是顺铂(IC_(50)=31.0±5.50μM)的20倍以上.机制研究表明,二氯二苯丁酸氮芥二氨合铂(Ⅳ)在细胞分裂周期中通过阻滞细胞分裂的G1期诱导细胞凋亡.In this paper, chlorambucil-platinum(Ⅳ) complex was synthesized and characterized by NMR and mass spectrometry. Cell-based in vitro studies revealed that chlorambucil-platinum(Ⅳ) exhibited potent cytotoxic activities against all the tested cancer cell lines, such as colorectal cancer LoVo, gastric cancer 7901, and lung cancer A549. Of note, in cisplatin-resistant A549-R cancer cells, chlorambucil-platinum(Ⅳ) complex still showed potent cytotoxicity with IC50 value of 1.33±0.09 μM, which was approximately 20-fold more potent than cisplatin(IC50=31.0±5.50 μM). Mechanistic studies revealed that chlorambucil-platinum(Ⅳ) induced cell apoptosis mainly through G1 phase cell cycle arrest. Overall, this study enhanced our understanding of platinum(Ⅳ)-based metallodrugs and helped to further study their therapeutic potential in cancer treatment.

关 键 词：四价铂 苯丁酸氮芥 抗癌活性 周期阻滞 凋亡 

分 类 号：O641.4[理学—物理化学]