Potential Chemopreventive Agents Based on the Structure of the Lead Compound 2-Bromo-1-hydroxyphenazine, Isolated from Streptomyces Species, Strain CNS284

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• 作者：Martin Conda-Sheridan ; Laura Marler ; Eun-Jung Park ; Tamara P. Kondratyuk ; Katherine Jermihov ; Andrew D. Mesecar ; John M. Pezzuto ; Ratnakar N. Asolkar ; William Fenical ; Mark Cushman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：December 23, 2010
• 年：2010
• 卷：53
• 期：24
• 页码：8688-8699
• 全文大小：932K
• 年卷期：v.53,no.24(December 23, 2010)
• ISSN：1520-4804

文摘

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.