Thiol-Based Probe for Electrophilic Natural Products Reveals That Most of the Ammosamides Are Artifacts

详细信息    查看全文

• 作者：Daniela Reimer ; Chambers C. Hughes
• 刊名：Journal of Natural Products
• 出版年：2017
• 出版时间：January 27, 2017
• 年：2017
• 卷：80
• 期：1
• 页码：126-133
• 全文大小：409K
• ISSN：1520-6025

文摘

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.