Thiol-based probe for electrophilic natural products reveals that most of the ammosamides are artifacts

TitleThiol-based probe for electrophilic natural products reveals that most of the ammosamides are artifacts
Publication TypeJournal Article
Year of Publication2017
AuthorsReimer D., Hughes CC
JournalJournal of Natural Products
Volume80
Pagination126-133
Date Published2017/01
ISBN Number0163-3864
Accession NumberWOS:000393089600017
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.

DOI10.1021/acs.jnadprod.6b00773
Short TitleJ. Nat. Prod.
Student Publication: 
No