title: Thiol-Based Probe for Electrophilic Natural Products Reveals That Most of the Ammosamides Are Artifacts.
abstract: To date, 16 members of the ammosamide family of natural products have been discovered, and except for ammosamide D each of these metabolites is characterized by an unusual chlorinated pyrrolo[4,3,2-de]quinoline skeleton. Several ammosamides have been shown to inhibit quinone reductase 2, a flavoenzyme responsible for quelling toxic oxidative species in cells or for killing cancer cells outright. Treatment of the extract from an ammosamide-producing culture (Streptomyces strain CNR-698) with a thiol-based reagent designed to label electrophilic natural products produced an ammosamide C-thiol adduct. This observation led us to hypothesize, and then demonstrate through experimentation, that all of the other ammosamides are derived from ammosamide C via nonenzymatic processes involving exposure to nucleophiles, air, and light. Like many established electrophilic natural products, reaction with the thiol probe suggests that ammosamide C is itself an electrophilic natural product. Although ammosamide C did not show substantial cytotoxicity against cancer cells, its activity against a marine Bacillus bacterial strain may reflect its ecological role.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego , La Jolla, California 92093-0204, United States.
authors.forename: Daniela
authors.initials: D
authors.lastname: Reimer
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego , La Jolla, California 92093-0204, United States.
authors.forename: Chambers C
authors.identifier: 0000-0002-7000-6438
authors.initials: CC
authors.lastname: Hughes
mesh_terms: D000577:Amides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013302:Streptomyces / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D001688:Biological Products; D006574:Heterocyclic Compounds, 2-Ring; D006575:Heterocyclic Compounds, 3-Ring; D011804:Quinolines; D013438:Sulfhydryl Compounds; C549633:ammosamide C; C573446:ammosamide D