Flavonoids enzyme inhibitors

The subject of flavonoids is taken up in Ebadi s Chapter 29, some of which are said to be effective against breast cancer. Varions subclasses are listed, and then-antioxidant properties are noted, along with their role as enzyme inhibitors. The chemical compound quercetin is singled ont as among the most active, and it is commonly found in onion, apples, kale, red wine, and green/black teas. A rednced risk of not only of breast cancer, but also of prostate, lung, colon, and stomach cancers is associated with an increased intake of fruits, vegetables, and soy prodncts. 

Lee H, Wang HW, Su HY, Hao NJ. The structure-activity relationships of flavonoids as inhibitors of cytochrome P450 enzymes in rat liver microsomes and the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline. Mutagenesis 1994 9 101-106. 

Mora A, Paya M, Rios JL, Alcaraz MJ. Structure-activity relationships of polymethoxyflavones and other flavonoids as inhibitors of non-enzymic hpid peroxidation. Biochem Pharmacol 1990 40 793-797. 

Klopman G, Dimayuga ML (1988) ComputCT-automated structure evaluation of flavonoids and other structurally related compounds as glyoxalase I enzyme inhibitors. Mol Pharmacol... 

Pairoba, C.F., Colombo, S.L. Andreo, C.S. (1996). Flavonoids as inhibitors of NADP-malic enzyme and PEP carboxylase from two C4 plants. Biosciences, Biotechnology and Biochemistry, 60, 779-783. 

The activity of flavonoids as inhibitors of the viral enzyme reverse transcriptase also suggests that they may be beneficial in the control of retroviral infections such as AIDS. 

Tiburzy (22,31) obtained similar results by application of the PAL inhibitor aminooxyacetic acid (AOA). However, AOA does not specifically inhibit PAL (99), and PAL is not only involved in lignin biosynthesis (100). Thus, AOA and the related inhibitor aminooxyphenyl propionic acid (AOPP) (101,102) inhibit the biosynthesis of lignin (103,104), anthocyanins (105), other flavonoids (106), and conjugates of cinnamic acids (107) via PAL, as well as ethylene (108-110) via a pyridoxal phosphate dependent enzyme (110,111). In view of the possible function of phenolic compounds as phytoalexins (21,112,113) and the well documented role of ethylene in some resistance reactions (114-116), the above cited experiments with AOA (22,... 

Flavonoids, especially flavones and flavonols, also directly bind to several CYP isoforms (lAl, 1A2, IBl, 3A4) involved in xenobiotics metabolism and inhibit enzyme activity. Structure-activity relationships show rather high isoform selectivities depending on the flavonoid substitution pattern and contrasted inhibition mechanisms. For instance, inhibition by flavonoids of 7-methoxyresorufin O-demethylation in microsomes enriched in CYP lAl and 1A2 reveals that galangin (3,5,7-trihydroxyflavone) is a mixed inhibitor of CYP 1A2 (.ST = 8 nM) and a five times less potent inhibitor of CYP 1A1. By contrast, 7-hydroxy flavone is a competitive inhibitor of CYP lAl (Aii = 15 nM) and a six times less potent inhibitor of CYP 1A2. In addition, fairly selective inhibition of CYP IBl (specifically detected in cancer cells) by some flavonoids has been reported. For example, 5,7-dihydroxy-4 -methoxyflavone inhibits IBl, 1 Al, and 1A2 with IC50 values of 7, 80, and 80 nM, respectively. ... 

Free radical scavengers inactivate LOXs by the interaction with their free radical intermediates or by reducing the enzyme active ferric form to inactive ferrous form. It has been shown that flavonoids, typical free radical scavengers are the effective inhibitors of neutrophil... 

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