抗癌先导化合物JS-K的哌嗪和高哌嗪类似物的合成与评价
Synthesis and evaluation of piperazine and homopiperazine analogues of JS-K, an anti-cancer lead compound.
作者信息
Nandurdikar Rahul S, Maciag Anna E, Citro Michael L, Shami Paul J, Keefer Larry K, Saavedra Joseph E, Chakrapani Harinath
机构信息
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702, USA.
出版信息
Bioorg Med Chem Lett. 2009 May 15;19(10):2760-2. doi: 10.1016/j.bmcl.2009.03.115. Epub 2009 Mar 28.
Abstract
Here we report a number of novel JS-K structural analogues with sub-micromolar anti-proliferative activities against human leukemia cell lines HL-60 and U937; JS-K is the anti-cancer lead compound O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. The ability of these compounds to generate intracellular nitric oxide correlated well with their observed anti-proliferative effects: analogues that had potent inhibitory activity against leukemia cells formed elevated levels of intracellular nitric oxide.
摘要
在此，我们报告了一些新型的JS-K结构类似物，它们对人白血病细胞系HL-60和U937具有亚微摩尔级的抗增殖活性；JS-K是抗癌先导化合物O(2)-(2,4-二硝基苯基)1-[(4-乙氧羰基)哌嗪-1-基]重氮-1,2-二醇盐。这些化合物产生细胞内一氧化氮的能力与其观察到的抗增殖作用密切相关：对白血病细胞具有强效抑制活性的类似物会形成较高水平的细胞内一氧化氮。
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