Synthesis and anticancer activity of dichloroplatinum(II) complexes of podophyllotoxin

被引:41
作者
Liu, Xuan [1 ]
Zhang, Lin-Lin [1 ]
Xu, Xiao-Hui [1 ]
Hui, Lin [2 ,3 ]
Zhang, Jin-Bang [5 ]
Chen, Shi-Wu [1 ,4 ]
机构
[1] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China
[2] Lanzhou Mil Command, Gen Hosp, Ctr Med Expt, Lanzhou 730050, Peoples R China
[3] Lanzhou Mil Command, Gen Hosp, Key Lab Stem Cells & Gene Drug Gansu Prov, Lanzhou 730050, Peoples R China
[4] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China
[5] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Peoples R China
关键词
Cisplatin; Podophyllotoxin; Microtubules inhibition; DNA cleavage; BIOLOGICAL EVALUATION; DERIVATIVES; CISPLATIN; AGENTS; DRUGS; 5-FU;
D O I
10.1016/j.bmcl.2013.04.089
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
A series of dichloroplatinum(II) complexes of podophyllotoxin (PPT) were prepared, and their cytotoxicity against sensitive (A-549, HeLa, HCT-8, Hep-G2, K562) and resistant (ADM/K562) cell lines were evaluated. Complex cis-[4 alpha-O-(2 '',3 ''-diaminopropanoyl)-podophyllotoxin] dichloride platinum(II) (12) displayed most potent cytotoxicity with IC50 value in the range 0.071-2.98 mu M. Complex 12 induces cell cycle arrest in the G(2)/M phase, and inhibits the formation of microtubules in HeLa cells. Furthermore, this complex exhibits potent DNA cleavage capabilities. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3780 / 3784
页数:5
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