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.
Keywords:
NFκB; apoptosis; chemoprevention; inflammation; lavanducyanin; phenazines.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification*
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Anti-Inflammatory Agents, Non-Steroidal / metabolism
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Antibiotics, Antineoplastic / chemistry
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Antibiotics, Antineoplastic / isolation & purification
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Antibiotics, Antineoplastic / metabolism
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Antibiotics, Antineoplastic / pharmacology
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Anticarcinogenic Agents / chemistry
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Anticarcinogenic Agents / isolation & purification*
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Anticarcinogenic Agents / metabolism
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Anticarcinogenic Agents / pharmacology*
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Apoptosis / drug effects
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Aquatic Organisms / metabolism*
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Cell Line, Transformed
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Drug Discovery
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Fermentation
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G1 Phase / drug effects
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Gene Expression Regulation, Enzymologic / drug effects
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HL-60 Cells
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Humans
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Inhibitory Concentration 50
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Leukemia, Promyelocytic, Acute / drug therapy
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Phenazines / chemistry
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Phenazines / isolation & purification*
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Phenazines / metabolism
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Phenazines / pharmacology*
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Streptomyces / metabolism*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antibiotics, Antineoplastic
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Anticarcinogenic Agents
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Phenazines
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lavanducyanin