Novel Marine Phenazines As Potential Cancer Chemopreventive and Anti-inflammatory Agents

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2012 Mar 14

PMID 22412812

Citations 38

Authors

Tamara P Kondratyuk

Eun-Jung Park

Rui Yu

Richard B van Breemen

Ratnakar N Asolkar

Brian T Murphy

William Fenical

John M Pezzuto

Affiliations

Soon will be listed here.

Abstract

Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC₅₀ values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC₅₀ values of >48.6, 15.1, and 8.0 μM, respectively). PGE₂ production was blocked with greater efficacy (IC₅₀ values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects.

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