title: Potential chemopreventive agents based on the structure of the lead compound 2-bromo-1-hydroxyphenazine, isolated from Streptomyces species, strain CNS284.
abstract: The isolation of 2-bromo-1-hydroxyphenazine from a marine Streptomyces species, strain CNS284, and its activity against NF-κB, suggested that a short and flexible route for the synthesis of this metabolite and a variety of phenazine analogues should be developed. Numerous phenazines were subsequently prepared and evaluated as inducers of quinone reductase 1 (QR1) and inhibitors of quinone reductase 2 (QR2), NF-κB, and inducible nitric oxide synthase (iNOS). Several of the active phenazine derivatives displayed IC₅₀ values vs QR1 induction and QR2 inhibition in the nanomolar range, suggesting that they may find utility as cancer chemopreventive agents.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and The Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Conda-Sheridan
authors.forename: Laura
authors.initials: L
authors.lastname: Marler
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: Katherine
authors.initials: K
authors.lastname: Jermihov
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Ratnakar N
authors.initials: RN
authors.lastname: Asolkar
authors.forename: William
authors.initials: W
authors.lastname: Fenical
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059001:Aquatic Organisms; D002460:Cell Line; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011808:Quinone Reductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C555227:2-bromo-1-hydroxyphenazine; D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D010619:Phenazines; D052247:Nitric Oxide Synthase Type II; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases