Thiol-Based Probe for Electrophilic Natural Products Reveals That Most of the Ammosamides Are Artifacts.
J Nat Prod
; 80(1): 126-133, 2017 01 27.
Article
em En
| MEDLINE
| ID: mdl-28055208
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Streptomyces
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Compostos de Sulfidrila
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Produtos Biológicos
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Amidas
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Compostos Heterocíclicos com 2 Anéis
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Compostos Heterocíclicos com 3 Anéis
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article