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

Abstract

The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces sp., strain CNS284, and its activity against NFκB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues 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 IC 50 values vs. QR1 induction and QR2 inhibition in the nanomolar range, suggesting they may find utility as cancer chemopreventive agents.

Marinocyanins, cytotoxic bromo-phenazinone meroterpenoids from a marine bacterium from the streptomycete clade MAR4

“…Known compounds 7 – 9 were identified as 2-bromo-1-hydroxyphenazine, 6,7 WS-9659A 14 (lavanducyanin) and the C-2 chlorinated analog WS-9659B 14 by comparison with their reported spectroscopic data. Spectroscopic data for 7 and 8 can be found in the Supplemental Information.…”

Isolation and structural identification of two bioactive phenazines from Streptomyces griseoluteus P510

“…The HPLC chromatogram and absorption spectrum of Compound 2 are shown in Fig . 2(2A, 2B) indicate that Compound 2 is 1-OH-PHZ [24], as shown in Table 3. Based on mass spectra, absorption spectra, and NMR data, Compound 2 from S. griseoluteus P510 is identified as 1-OH-PHZ (Fig.…”

Phenazine as an Anticancer Agent

“…Recently, Conda-Sheridan and coworkers (Conda-Sheridan et al 2010) have isolated 2-bromo-1-hydroxyphenazine (6, Fig. 11.2) from a marine Streptomyces species (strain CNS284) and demonstrated anti NF-KappaB activity.…”

“…For example, transcriptional regulation of NF-jB has been intensely studied. The transcription factor nuclear factor kappa-light chain of activated B cells (NF-jB) and, the inducible nitric oxide synthase (iNOS), are potential chemopreventive target along with Phase I (aromatase, quinone reductase 2 (QR2) and Phase II (QR1, glutathione-S-transferase (GST) enzymes that detoxify carcinogens) (Conda-Sheridan et al 2010).…”

“…In principle, agents that can suppress NF-jB activation and iNOS have the potential of suppressing carcinogenesis (Inoue et al 2007;Konryatuk et al 2012). Recent study have showed that 2-bromo-1-hydroxyphenazine (Conda-Sheridan et al 2010) and 2-bromo-N-substituted monoterpene phenazine and 2-bromo-N-substituted isoprenylated phenazine (Kondryatuk et al 2012), as well as several phenazine derivatives, displayed IC 50 value versus QR1 induction and QR2 inhibition in the nanomolar range, suggesting some of them as cancer chemopreventive agents (Conda-Sheridan et al 2010;Cimmino et al 2012).…”