Novel marine phenazines as potential cancer chemopreventive and anti-inflammatory agents.

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.

• Authors: Tamara P Kondratyuk, Eun-Jung Park, Rui Yu, Richard B Van Breemen, Ratnakar N Asolkar, Brian T Murphy, William Fenical, John M Pezzuto
• Journal: Marine drugs (Mar Drugs) Vol. 10 Issue 2 Pg. 451-464 (Feb 2012) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 22412812 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antibiotics, Antineoplastic
• Anticarcinogenic Agents
• Phenazines
• lavanducyanin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, isolation & purification, metabolism, pharmacology)
• Antibiotics, Antineoplastic (chemistry, isolation & purification, metabolism, pharmacology)
• Anticarcinogenic Agents (chemistry, isolation & purification, metabolism, pharmacology)
• Apoptosis (drug effects)
• Aquatic Organisms (metabolism)
• Cell Line, Transformed
• Drug Discovery
• Fermentation
• G1 Phase (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• HL-60 Cells
• Humans
• Inhibitory Concentration 50
• Leukemia, Promyelocytic, Acute (drug therapy)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• Phenazines (chemistry, isolation & purification, metabolism, pharmacology)
• Streptomyces (metabolism)