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

A number of structural analogues of JS-K, an anti-cancer lead compound, with nearly identical anti-proliferative activities are reported. 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-...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-05, Vol.19 (10), p.2760-2762
Main Authors: Nandurdikar, Rahul S., Maciag, Anna E., Citro, Michael L., Shami, Paul J., Keefer, Larry K., Saavedra, Joseph E., Chakrapani, Harinath
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Azo Compounds - chemical synthesis
Azo Compounds - chemistry
Azo Compounds - pharmacology
Biological and medical sciences
Cancer
Cell Line, Tumor
Diazeniumdiolate
General aspects
Glutathione
Glutathione S-transferase
Homopiperazine
Humans
JS-K
Medical sciences
Nitric oxide
Nitric Oxide - metabolism
Pharmacology. Drug treatments
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacology
Prodrug
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Summary:A number of structural analogues of JS-K, an anti-cancer lead compound, with nearly identical anti-proliferative activities are reported. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.03.115