Synthesis and antitumor activity of iodo-bridged binuclear platinum complex  

作　　者：ZHANG Jinchao GONG Yuqiu ZHENG Xiaoming YANG Mengsu CUI Jingrong 

机构地区：[1]Department of Chemistry, College of Chemistry & Environmental Science, Hebei University, Baoding 071002, China [2]Department of Chemistry, Zhejiang University, Hangzhou 310028, China [3]Department of Biology and Chemistry, City University of Hong Kong, Hong Kong, China [4]State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China

出　　处：《Chinese Science Bulletin》2006年第8期911-917,共7页

基　　金：supported by the Natural Science Foundation of Zhejiang Province(Grant No.298068);the 0pening Foundation of State Key Laboratory of Natural and Biomimetic Drugs,Peking University.

摘　　要：Iodo-bridged binuclear platinum(II) com- plex[Pt( -NH2)I2]2(BPA) has been synthesized and characterized by elemental analysis, conductivity, differential thermal analysis, IR, UV and 1HNMR spectra techniques. The cytotoxicity of the complex was tested by MTT and SRB assays. The results show that complex BPA demonstrates better cyto-toxicity than that of the clinically established cisplatin against EJ, HCT-8, BGC-823, HL-60 and MCF-7 cell lines. The complex BPA at concentrations of 1.00 and 2.00 μmol/L induces G1 cell cycle arrest in HL-60 cells. The level of total platinum bound to DNA in HL-60 cells is significantly higher than that of cisplatin under the same experimental conditions. Acute tox-icity experimental results indiacte that LD50 of BPA is 815.3 mg/kg by intraperitoneal administration. BPA at dose of 12 mg/kg significantly inhibits the growth of nude mice implanted by human A2780 and HCT-116 carcinomas, and inhibition rate is similar to that of cisplatin at dose of 4 mg/kg by intraperitoneal admini-stration. BPA at dose of 20 mg/kg inhibits the growth of nude mice implanted by human A549 carcinomas, but there was no significant statistical difference.Iodo-bridged binuclear platinum（Ⅱ） complex[Pt（ -NH2）l2]2（BPA） has been synthesized and characterized by elemental analysis, conductivity, differential thermal analysis, IR, UV and ^1HNMR spectra techniques. The cytotoxicity of the complex was tested by MTT and SRB assays. The results show that complex BPA demonstrates better cytotoxicity than that of the clinically established cisplatin against EJ, HCT-8, BGC-823, HL-60 and MCF-7 cell lines. The complex BPA at concentrations of 1.00 and 2.00μmol/L induces G1 cell cycle arrest in HL-60 cells. The level of total platinum bound to DNA in HL-60 cells is significantly higher than that of cisplatin under the same experimental conditions. Acute toxicity experimental results indiacte that LD50 of BPA is 815.3 mg/kg by intraperitoneal administration. BPA at dose of 12 mg/kg significantly inhibits the growth of nude mice implanted by human A2780 and HCT-116 carcinomas, and inhibition rate is similar to that of cisplatin at dose of 4 mg/kg by intraperitoneal administration. BPA at dose of 20 mg/kg inhibits the growth of nude mice implanted by human A549 carcinomas, but there was no significant statistical difference.

关 键 词：抗肿瘤活性 合成 双核铂复合物 细胞周期 抗癌抗菌素 

分 类 号：R979.1[医药卫生—药品]