Synthesis and evaluation of piperazine and homopiperazine analogues of JS-K, an anti-cancer lead compound

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Nandurdikar, Rahul S.²  Maciag, Anna E.¹  Citro, Michael L.¹  Shami, Paul J.³  Keefer, Larry K.²  Saavedra, Joseph E.¹  Chakrapani, Harinath² 

[1] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA

[2] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA

[3] Univ Utah, Div Oncol, Dept Internal Med, Salt Lake City, UT 84112 USA

关键词: Nitric oxide;    JS-K;    Cancer;    Prodrug;    Glutathione;    Glutathione S-transferase;    Homopiperazine;    Diazeniumdiolate;   

DOI  :  10.1016/j.bmcl.2009.03.115

来源: Elsevier

【 摘 要 】

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. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free