Structure and antioxidant activity of brominated flavonols and flavanones.
Hypobromous acid (HOBr) produced by both eosinophil peroxidase (EPO) and myeloperoxidase (MPO) is a stronger oxidant than HOCl, and is also essential for optimal and efficient microbial killing. Considering the potential cytotoxic effect of HOBr, if it is formed outside the phagosome, it should be useful to scavenge it in order to protect the nearby tissues. In this study the ability of selected flavonoids to protect against HOBr mediated oxidation reactions was performed through a competitive reaction, and the resulting products identified by high performance liquid chromatography (HPLC) and electrospray ionization tandem mass spectrometry(ESI-MS/MS). Several structural features were found to be important to confer high antioxidant activity to flavonoids towards HOBr: the C2=C3 double bond and the 3-OH group in the C-ring, and the presence of both 5-OH and 7-OH groups in the A-ring. The MS results showed that flavonoids are dibrominated in the A-ring, suggesting that (except for fisetin) bromination occurs at C6 and C8 positions, through an electrophilic aromatic substitution reaction. The chemical modifications achieved by bromination of flavonoids have changed their biological properties, presenting their brominated derivatives higher antioxidant activity, as radical scavengers, and higher lipophilicity, than the parent flavonoids. Brominated flavonoids may then diffuse easily through membranes increasing the intracellular concentration of the compounds. These locally formed metabolites may also interact with signaling cascades involving cytokines and regulatory transcription factors, thus playing a role in inflammation and in the regulation of immune response.
Justino
Gonçalo C
GC
CQB/DQB, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
Rodrigues
Margarida
M
Florêncio
M Helena
MH
Mira
Lurdes
L
D001959:Bromates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D044950:Flavanones / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry; D044948:Flavonols / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry*; D015394:Molecular Structure; D016877:Oxidants / Q000737:chemistry*; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry; D012431:Rutin / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D047309:Flavones
D001959:Bromates; D044950:Flavanones; D005419:Flavonoids; D044948:Flavonols; D016166:Free Radical Scavengers; D016877:Oxidants; D011794:Quercetin; D012431:Rutin; C008548:morin; D047309:Flavones; C003377:taxifolin; C027664:hypobromous acid; C005273:naringenin; C005274:naringin