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

Marine Drugs

Tamara P. Kondratyuk²  Eun-Jung Park²  Rui Yu¹  Richard B. van Breemen¹  Ratnakar N. Asolkar³  Brian T. Murphy¹  William Fenical³ 

[1] Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA;College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA;Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093, USA;

关键词: apoptosis;    chemoprevention;    inflammation;    NFκB;    phenazines;    lavanducyanin;   

DOI  :  10.3390/md10020451

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.