Potential chemopreventive agents based on the structure of the lead compound 2-bromo-1-hydroxyphenazine, isolated from Streptomyces species, strain CNS284

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.