ABSTRACT
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.
Subject(s)
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/metabolismABSTRACT
Fourteen new natural products, namely, 2-[(Z)-styryl]-5-geranylresorcin-1-carboxylic acid (1), amorfrutin D (2), 4-O-demethylamorfrutin D (3), 8-geranyl-3,5,7-trihydroxyflavanone (4), 8-geranyl-5,7,3'-trihydroxy-4'-methoxyisoflavone (5), 6-geranyl-5,7,3'-trihydroxy-4'-methoxyisoflavone (6), 8-geranyl-7,3'-dihydroxy-4'-methoxyisoflavone (7), 3-O-demethyldalbinol (8), 6a,12a-dehydro-3-O-demethylamorphigenin (9), (6aR,12aR,5'R)-amorphigenin (10), amorphispironones B and C (11 and 12), resokaempferol 3-O-ß-d-glucopyranosyl-(1â2)-ß-d-glucopyranoside-7-O-α-l-rhamnopyranoside (13), and daidzein 7-O-ß-d-glucopyranosyl-(1â2)-ß-d-glucopyranoside (14), together with 40 known compounds, were isolated from the fruits of Amorpha fruticosa. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic analysis as well as from the mass spectrometry data. ECD calculations were performed to determine the absolute configurations of 11 and 15. Compounds 1, 4-6, and 16-23 showed potent to moderate antibacterial activities against several Gram-positive bacteria with MIC values ranging from 3.1 to 100 µM. In addition, compounds 11 and 24-33 were significantly cytotoxic against the L5178Y mouse lymphoma cell line and exhibited IC50 values from 0.2 to 10.2 µM.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Fabaceae/chemistry , Fruit/chemistry , Isoflavones/isolation & purification , Lymphoma/drug therapy , Phenols/chemistry , Plant Extracts/isolation & purification , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Inhibitory Concentration 50 , Isoflavones/chemistry , Isoflavones/pharmacology , Lymphoma/chemistry , Mice , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
The first chemical examination of roots of the traditionally used medicinal plant Talinum triangulare (Portulacaceae) from Nigeria led to the isolation of two new C-methylated flavonoids, 5,6-dimethoxy-7-hydroxy-8-methyl-flavone (1), 5,6-dimethoxy-8-methyl-2-phenyl-7H-1-benzopyran-7-one (2), and one new α-pyrone derivative, 4-methoxy-6-(2-hydroxy-4-phenylbutyl)-2H-pyran-2-one (3), along with thirteen known compounds, including nine amides (4-12), indole-3-carboxylic acid (13), p-hydroxy benzoic acid (14), and two steroids (15-16). Their structures were elucidated by extensive spectroscopic measurements including 1D, 2D NMR, MS, and by comparison with the literature. All isolated compounds were screened for their cytotoxic and antifungal activities. However, none of them showed significant activity.
Subject(s)
Flavonoids/chemistry , Plant Roots/chemistry , Portulacaceae/chemistry , Pyrones/chemistry , Animals , Cell Line, Tumor , Flavonoids/isolation & purification , Mice , Molecular Structure , Nigeria , Plants, Medicinal/chemistry , Pyrones/isolation & purificationABSTRACT
Stellaria nemorum L. and S. holostea L. (Caryophyllaceae) were investigated for their flavonoids. The new flavonoid 6-C-[(α-arabinopyranosyl)-( 1-->2)-O-ß- xylopyranosyl]apigenin (1) and the four known C-glycosides, 6-C-[(α-arabinopyranosyl)-(1-->2)-O-ß-glucopyranosyl]apigenin (2), apigenin 6-C-ß- galactopyranoside-8-C-ß-glucopyranoside (3), apigenin 6-C-ß-glucopyranoside-8-C-α-arabinopyranoside (4), and apigenin 6-C-ß-glucopyranoside-8-C-ß- xylopyranoside (5) were isolated from the aerial parts of S. nemorum for the first time. Furthemore, five known flavonoids, 3,5,7-trihydroxy-3',5'- dimethoxyflavone (9), diosmetin 6-C-ß-glucopyranoside (8), schaftoside (4), isoorientin (6) and orientin (7) were obtained from the aerial parts of S. holostea. Compounds 4, 8 and 9 are reported for the first time from this species. The structures of all isolated compounds were unambiguously elucidated by one- and two- dimensional NMR and mass spectral analysis, by acid hydrolysis, as well as by comparison with literature data. The crude extracts of the investigated species exhibited antimicrobial activity against Staphylococcus aureus, while none of the isolated compounds was found to be active.
