Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

✍ Scribed by Kondratyuk, Tamara P.; Park, Eun-Jung; Yu, Rui; van Breemen, Richard B.; Asolkar, Ratnakar N.; Murphy, Brian T.; Fenical, William; Pezzuto, John M.

• Book ID: 120344637
• Publisher: MDPI Publishing
• Year: 2012
• Tongue: English
• Weight: 407 KB
• Volume: 10
• Category: Article
• ISSN: 1660-3397
• DOI: 10.3390/md10020451

✦ Synopsis

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 (IC~50~ values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC~50~ values of >48.6, 15.1, and 8.0 μM, respectively). PGE~2~ production was blocked with greater efficacy (IC~50~ 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.