3.5.7- Trihydroxyflavones

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. ... 

Eventually, flavonoids can be hydroxylated or demethylated by CYPs. For instance, hesperetin (4 -methoxy-3, 5,7-trihydroxyflavanone) is specifically demethylated by CYPs lAl and IBl, but not by CYPs 1A2 and 3A4. In addition, 3,5,7-trihydroxyflavone undergoes sequential CYP lAl-catalyzed hydroxylation at C4 and C3 to finally yield querce-tin. These reactions may be relevant to flavonoid metabolism and cytotoxicity since the corresponding products are more reducing and thus more prone to autoxidation with simultaneous ROS production. 

Trihydroxyflavone (galangin) 3-Glucoside-8-sulfate Phyllanthus virgatus whole plant Euphorbiaceae 165... 

Some bioactive flavonols include aldose reductase inhibitors (axillarin (5,7,3, 4 -tetrahy-droxy-6-methoxyflavone), 2,3-dihydroquercetin (taxifolin), 6-hydroxykaempferol (galetin), hyperin (quercetin 3-0-galactoside), isoquercetrin, morin (3,5,7,2, 4 -pentahydroxy-flavone), quercetin, quercitrin and rutin) anti-inflammatory 5-LOX inhibitors (fisetin (3,7,3, 4 -tetrahydroxyflavone), kaempferol, morin, myricetin, quercetin and rutin) a GOX inhibitor (galangin (3,5,7-trihydroxyflavone)) iodothyronine deiodinase inhibitors (fisetin, kaempferol and morin) NADH and succinate dehydrogenase inhibitors (fisetin and myricetin) and protein kinase inhibitors (fisetin, galangin, isorhamnetin, kaempferide... 

Forsythiaside (= Forsythoside A) (phenylpropanoid glycoside) Galangin (= 3,5,7-Trihydroxyflavone)... 

The most widespread flavonoids reported in the Baccharis genus are flavones, but flavonols and flavanones have also been isolated. For example, Kupchan and Baverschmidt [74] reported the isolation and identification of two methylated flavonols, 3,4 -dimethoxy-3 ,5,7-trihydroxyflavone, Fig. (43) and centaureidin, Fig. (44) from B. sarolhroides. 

Essential oil obtained from the fresh rhizomes oiA. conchigera showed the presence of twelve terpenoids by GC-MS analysis, and the major component was chavicol acetate [44]. 1-Hydroxychavicol acetate [45], 4-acetoxycinnamyl alcohol and 4-acetoxycinnamyl acetate [46] were isolated from the aqueous layer obtained from the steam distillation of the rhizomes. Phenylpropanoid derivatives, chavicol acetate and eugenol acetate were present in the fruit of the plant [47]. In addition to four known diaryIheptanoids 40,41,43 and 44, and two known flavonoids, 3,5,7-trihydroxyflavone and 3,5,7-trihydroxy-4 -methoxyflavone, a new diarylheptanoid 54 was isolated from the rhizomes of the same plant [48]. 

From alnusin trimethyl ether (3,5,6,7-tetramethoxyflavone) (m.p. 112-112°5) (SM) refluxing in a mixture of 50% potassium hydroxide solution and ethanol for 20 h under nitrogen (50%). SM was prepared by methylation of alnusin (6-methoxy-3,5,7-trihydroxyflavone) (m.p. 239-241°). Alnusin was the main flavonoid isolated from Alnus sieboldiana (Betulaceae) [4971] ... 

Alnusin. 6-Methoxy-3,5,7-trihydroxyflavone, 1337 Alnusin trimethyl ether. 3,5,6,7-Tetramethoxyflavone, 1337 o-Anisidine. 2-Methoxyaniline, 1237 m-Anisidine. 3-Methoxyaniline, 1237 p-Anisidine. 4-Methoxyaniline, 1237... 

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