替莫唑胺四价铂配合物的合成及抗肿瘤性能  

Synthesis and Antitumor Properties of Temozolomide-Based Platinum(Ⅳ) Complexes

作　　者：苏岩 王萌萌 刘红科[1] 苏志 SU Yan;WANG Meng-Meng;LIU Hong-Ke;SU Zhi(School of Chemistry and Materials Science,Nanjing Normal University,Nanjing 210023,China)

机构地区：[1]南京师范大学化学与材料科学学院,南京210023

出　　处：《无机化学学报》2022年第3期430-440,共11页Chinese Journal of Inorganic Chemistry

基　　金：国家自然科学基金(No.21771109,21778033,21977052);江苏省特聘教授基金资助。

摘　　要：替莫唑胺是临床上治疗胶质瘤的一线药物。我们将替莫唑胺进行化学修饰,作为配体引入到四价铂配合物中,合成了2种新型四价铂配合物P1T和P2T,并利用核磁共振氢谱及碳谱对其进行了基础表征。研究结果表明,配合物具有良好的脂溶性和较快的水解速率。进一步使用MTT法、流式细胞术、共聚焦成像及蛋白免疫印迹法对P1T和P2T的抗肿瘤活性及诱导肿瘤细胞死亡机制进行了深入的探究。结果发现,配合物P1T和P2T对胶质瘤细胞株A261表现出了较高的细胞毒性,而对正常神经细胞HT-22毒性较小,表现出了较好的细胞选择性。流式细胞术揭示配合物P1T和P2T将细胞周期阻滞在G2/M期,导致DNA损伤,最终诱导肿瘤细胞凋亡。Temozolomide is the first-line anticancer drug for the clinical treatment of glioblastoma.In this work,temozolomide was chemically modified and introduced into the platinum(Ⅳ) complex.Two new Pt(Ⅳ) complexes P1T and P2T were successfully synthesized and characterized by ^(1)H NMR and ^(13)C NMR.The results show that both complexes had good lipid solubility with a fast hydrolysis rate.The anticancer activity and the mechanism of P1T and P2T were investigated with the MTT assay,flow cytometry,confocal imaging,and western blot.The results demonstrate that complexes P1T and P2T owned high cytotoxicity to glioma cell line A261,but low toxicity to normal nerve cell HT-22,indicating good cancer cell selectivity.Flow cytometry reveals that complexes P1T and P2T arrest the cell cycle in the G2/M phase,leading to DNA damage and ultimately inducing tumor cell apoptosis.

关 键 词：替莫唑胺 铂类配合物 胶质瘤 抗肿瘤药物 

分 类 号：O614.826[理学—无机化学]