Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound
Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound
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DOI：
10.1016/j.bmc.2007.11.035
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Saavedra, Joseph E.
中科院分区：
文献类型：
--
作者：
Chakrapani, Harinath;Wilde, Thomas C.;Saavedra, Joseph E.
二醇二氮鎓阴离子及其前药形式是一氧化氮（NO）的可靠来源，作为有前途的治疗剂已引起人们的兴趣。O-2-（2，4-二硝基-5-（4-（N-甲氨基）苯甲酰氧基）苯基）-1-（N，N-二甲氨基）二氮烯-1-鎓-1，2-二醇盐（PABA/NO）是一种抗癌先导化合物，被谷胱甘肽激活后释放NO，本文合成了其结构类似物。一氧化氮的释放模式，这些O-2-在谷胱甘肽存在下测试了（2，4-二硝基苯基）二醇二氮烯鎓盐，发现在没有竞争途径的情况下，这些化合物释放几乎定量的NO。测定了NO及其结构类似物抑制人白血病细胞增殖的作用，发现释放升高量的NO的化合物显示出上级细胞毒性作用。(C)2007爱思唯尔有限公司保留所有权利。
Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O-2-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl)-1-(N,N-dimetliylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O-2-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects. (C) 2007 Elsevier Ltd. All rights reserved.