Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation.
Anti-Bacterial Agents
/ pharmacology
Antibiotics, Antineoplastic
/ pharmacology
Antifungal Agents
/ pharmacology
Bacteria
/ drug effects
Cations
Cell Line
Chelating Agents
/ pharmacology
Copper
/ metabolism
Fungi
/ drug effects
Iron
/ metabolism
Leupeptins
/ pharmacology
Microbial Sensitivity Tests
Mutagenesis
Rifabutin
/ analogs & derivatives
Yeasts
/ drug effects
Journal
Journal of natural products
ISSN: 1520-6025
Titre abrégé: J Nat Prod
Pays: United States
ID NLM: 7906882
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
pubmed:
18
3
2020
medline:
22
6
2021
entrez:
18
3
2020
Statut:
ppublish
Résumé
Kendomycin is a small-molecule natural product that has gained significant attention due to reported cytotoxicity against pathogenic bacteria and fungi as well as a number of cancer cell lines. Despite significant biomedical interest and attempts to reveal its mechanism of action, the cellular target of kendomycin remains disputed. Herein it is shown that kendomycin induces cellular responses indicative of cation stress comparable to the effects of established iron chelators. Furthermore, addition of excess iron and copper attenuated kendomycin cytotoxicity in bacteria, yeast, and mammalian cells. Finally, NMR analysis demonstrated a direct interaction with cations, corroborating a close link between the observed kendomycin polypharmacology across different species and modulation of iron and/or copper levels.
Identifiants
pubmed: 32182062
doi: 10.1021/acs.jnatprod.9b00826
pmc: PMC7497661
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antibiotics, Antineoplastic
0
Antifungal Agents
0
Cations
0
Chelating Agents
0
Leupeptins
0
kendomycin
0
Rifabutin
1W306TDA6S
Copper
789U1901C5
Iron
E1UOL152H7
benzyloxycarbonylleucyl-leucyl-leucine aldehyde
RF1P63GW3K
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
965-971Références
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