The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria.

Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE

Publication: Oxford : Elsevier Science
Original Publication: Oxford : New York : Pergamon Press, c1993-

Anti-Bacterial Agents/*pharmacology ; Chalcone/*analogs & derivatives ; Gram-Positive Bacteria/*drug effects ; Gram-Positive Bacterial Infections/*drug therapy; Anti-Bacterial Agents/chemistry ; Cell Line ; Chalcone/chemistry ; Chalcone/pharmacology ; Fabaceae/chemistry ; Gram-Positive Bacteria/metabolism ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Methicillin-Resistant Staphylococcus aureus/metabolism ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/metabolism

Xanthoangelol is a geranylated chalcone isolated from fruits of Amorpha fructicosa that exhibits antibacterial effects at low micromolar concentration against Gram-positive bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecium and Enterococcus faecalis. We demonstrate that Xanthoangelol treatment of Gram-positive bacteria affects bacterial membrane integrity and leads to a leakage of intracellular metabolites. This correlates with a rapid collapse of the membrane potential and results in a fast and strong bactericidal effect. Proteomic profiling of Xanthoangelol-treated cells revealed signatures of cell wall and/or membrane damage and oxidative stress. Xanthoangelol specifically disturbs the membrane of Gram-positive bacteria potentially by forming pores resulting in cell lysis. In contrast, Xanthoangelol treatment of human cells showed only mildly hemolytic and cytotoxic effects at higher concentrations. Therefore, geranylated chalcones such as Xanthoangelol are promising lead structures for new antimicrobials against drug-resistant gram-positive pathogens.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)

Keywords: Amorpha fructicosa; Antibacterial activity; Chalcone; Cytotoxicity; Hemolysis; MRSA; Membrane; Phenolic metabolite; Xanthoangelol

0 (Anti-Bacterial Agents)
5S5A2Q39HX (Chalcone)
62949-76-2 (xanthoangelol)

Date Created: 20191026 Date Completed: 20200924 Latest Revision: 20200924

20240829

10.1016/j.bmc.2019.115151

31648878