Abstract
The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces species, strain CNS284, and its activity against NF-κB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues should be developed. Numerous phenazines were subsequently prepared and evaluated as inducers of quinone reductase 1 (QR1) and inhibitors of quinone reductase 2 (QR2), NF-κB, and inducible nitric oxide synthase (iNOS). Several of the active phenazine derivatives displayed IC₅₀ values vs QR1 induction and QR2 inhibition in the nanomolar range, suggesting that they may find utility as cancer chemopreventive agents.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Anticarcinogenic Agents / chemical synthesis*
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Anticarcinogenic Agents / chemistry
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Anticarcinogenic Agents / pharmacology
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Aquatic Organisms
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Cell Line
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Cell Line, Tumor
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Enzyme Induction
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Humans
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Mice
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NF-kappa B / antagonists & inhibitors
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Phenazines / chemical synthesis*
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Phenazines / chemistry
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Phenazines / pharmacology
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Quinone Reductases / antagonists & inhibitors
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Quinone Reductases / biosynthesis
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Streptomyces / chemistry*
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Structure-Activity Relationship
Substances
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2-bromo-1-hydroxyphenazine
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Anticarcinogenic Agents
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NF-kappa B
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Phenazines
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Nitric Oxide Synthase Type II
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NRH - quinone oxidoreductase2
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Quinone Reductases