Abstract
This Letter reports the synthesis and biological evaluation of a collection of aminophthalazines as a novel class of compounds capable of reducing production of PGE(2) in HCA-7 human adenocarcinoma cells. A total of 28 analogs were synthesized, assayed for PGE(2) reduction, and selected active compounds were evaluated for inhibitory activity against COX-2 in a cell free assay. Compound 2xxiv (R(1)=H, R(2)=p-CH(3)O) exhibited the most potent activity in cells (EC(50)=0.02 μM) and minimal inhibition of COX-2 activity (3% at 5 μM). Furthermore, the anti-tumor activity of analog 2vii was analyzed in xenograft mouse models exhibiting good anti-cancer activity.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopyridines / chemical synthesis*
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Aminopyridines / chemistry
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Aminopyridines / pharmacology*
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Dinoprostone / antagonists & inhibitors*
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Dinoprostone / biosynthesis
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Disease Models, Animal
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Enzyme Activation / drug effects
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Gene Expression Regulation / drug effects
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Humans
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Mice
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Molecular Structure
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Phthalazines / chemical synthesis*
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Phthalazines / chemistry
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Phthalazines / pharmacology*
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Transplantation, Heterologous
Substances
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5-aminophthalazine
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Aminopyridines
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Antineoplastic Agents
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Phthalazines
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Dinoprostone