title: 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.affiliation: College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.affiliation: College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Van Breemen
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Ratnakar N
authors.initials: RN
authors.lastname: Asolkar
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.|Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Murphy
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: William
authors.initials: W
authors.lastname: Fenical
authors.affiliation: College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059001:Aquatic Organisms / Q000378:metabolism*; D002461:Cell Line, Transformed; D055808:Drug Discovery; D005285:Fermentation; D016193:G1 Phase / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010619:Phenazines / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D016588:Anticarcinogenic Agents; D010619:Phenazines; C060460:lavanducyanin