高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

α,β-聚[N-(丁二酸基)-L-天冬酰胺]的合成及其顺铂大分子药物的细胞毒性

王成运, 公彦宝, 刘顺英, 罗淑芳, 黄进, 余家会   

  1. 华东师范大学新药创制先进技术研究院, 上海 200062
  • 收稿日期:2008-01-10 修回日期:1900-01-01 出版日期:2008-08-10 发布日期:2008-08-10
  • 通讯作者: 余家会

Synthesis of α,β-Poly[(N-succinyl)-L-aspartamide] and in vitro Cytotoxicity of Its cis-Dichlorodiammine Platinum Macromolecular Prodrug

WANG Cheng-Yun, GONG Yan-Bao, LIU Shun-Ying, LUO Shu-Fang, HUANG Jing, YU Jia-Hui*   

  1. Advanced Research Center of NBIC Integrated Drug Discovery and Development, East China Normal University, Shanghai 200062, China
  • Received:2008-01-10 Revised:1900-01-01 Online:2008-08-10 Published:2008-08-10
  • Contact: YU Jia-Hui

PDF (PC)

摘要： L-天冬氨酸在H2O/三乙胺混合溶剂中直接均相开环聚(L-天冬酰亚胺)(PSI), 合成α,β-聚[N-(丁二酸基)-L-天冬酰胺](PSAA). 研究了H2O和三乙胺的混合体积比对反应物溶解性能的影响, 并用FTIR和1H NMR表征了PSAA的结构. 以PSAA和α,β-聚(L-天冬氨酸)(PAsp)为载体, 与顺式二氯二氨合铂(Ⅱ)(CDDP)络合, 合成了PSAA-CDDP和PAsp-CDDP大分子药物. 结果表明, 载体PSAA和PAsp对Bel7402细胞的毒性均低于同浓度的聚赖氨酸; PSAA-CDDP的水溶性良好, 载药量较高, 达到了14.6%, 其药物控制释放性能较好; PSAA-CDDP和PAsp-CDDP的细胞毒性随着其浓度的增大而增大, 且细胞毒性PAsp-CDDP<PSAA-CDDP<CDDP.

关键词: α,β-聚(L-天冬氨酸), α,β-聚[N-(丁二酸基)-L-天冬酰胺], 顺铂, 大分子药物, 细胞毒性

Abstract: It is reported that conjugated CDDP to polymer carriers can effectively reduce drug's cytotoxicity. In this paper, α,β-poly[(N-succinyl)-L-aspart amide](PSAA) was successfully synthesized via ring cleavage reaction of L-asprtic acid to polysuccinmide in a homogeneous system at room temperature, with the aid of water/triethylamine as a mixed solvent, and characterized by FTIR and 1H NMR. The influence of volume ratios of water to triethylamine on the reaction was evaluated. PSAA-CDDP and PAsp-CDDP macromolecular prodrugs were prepared with conjugation of PSAA and α,β-poly(L-aspartic acid)(PAsp) with cis-dichlorodiammine platinum(CDDP), respectively. The results show that the cytotoxicity of PSAA or PAsp was rather low. The drugs could be released from PSAA-CDDP or PAsp-CDDP in a controllable manner. The in vitro cytotoxi-city of PSAA-CDDP or PAsp-CDDP against Bel-7402 cells increased with increasing dosage, but was lower than that of CDDP with the corresponding dosage. The cytotoxicity was ranked as PAsp-CDDP<PSAA-CDDP<CDDP.

Key words: α,β-Poly(L-aspartic acid), α,β-Poly[(N-succinyl)-L-aspartamide], cis-Dichlorodiammine platinum(Ⅱ), Macromolecular prodrug, Cytotoxicity

中图分类号: 

TrendMD: