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Mar. Drugs 2012, 10(2), 451-464; doi:10.3390/md10020451

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

1 College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA 2 Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA 3 Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093, USA
* Author to whom correspondence should be addressed.
Received: 27 December 2011 / Revised: 8 February 2012 / Accepted: 13 February 2012 / Published: 16 February 2012
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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: apoptosis; chemoprevention; inflammation; NFκB; phenazines; lavanducyanin apoptosis; chemoprevention; inflammation; NFκB; phenazines; lavanducyanin
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kondratyuk, T.P.; Park, E.-J.; Yu, R.; van Breemen, R.B.; Asolkar, R.N.; Murphy, B.T.; Fenical, W.; Pezzuto, J.M. Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents. Mar. Drugs 2012, 10, 451-464.

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