Flavonoids stmctures

Cao, G. Sofic, E. Prior, R.L. 1997. Antioxidant and prooxidant behavior of flavonoids Stmcture-activity relationships. Free Radic. Biol. Med. 22 749-760. 

The leaves of Camellia sinensis are similar to most plants in general morphology and contain all the standard enzymes and stmctures associated with plant cell growth and photosynthesis (10—12). Unique to tea plants are large quantities of flavonoids and methylxanthines, compounds which impart the unique flavor and functional properties of tea. The general composition of fresh tea leaves is presented ia Table 1. 

Additional information on chemical variation within this species came from studies of exudate and internal (vacuolar) pigments based on broader collections of the fern (Star et al., 1975a, b). Exudate flavonoids, identified from specimens representing the range of the species, were identified as ceroptene [221], the C-methylflavonol pityrogrammin [222], and two derivatives of kaempferol, the 4 -methyl ether [223] and the 7,4 -dimethyl ether [224] (see Fig. 2.69 for stmctures 221-224). 

Offen W, Martinez-Fleites C Yang M, Kiat-Lim E, Davis BG, Tarling CA, Ford C, Bowles DJ, Davies GJ (2006) Stmcture of a flavonoid glucosyltransferase reveals the basis for plant natural product modification. EMBO 1 25 1396-1405... 

Isoflavones, isoflavanones and neoflavonoids are also members of the flavonoid group. They all have the C6-C3-C6 stmcture but the B-ring is in a different position on the oxygen heterocycle. Examples are isoflavone (1.33) and the neoflavonoid dalbergin (1.34). 

The present work compiles the available literature about flavonoids inhibiting cancer cell lines and studies which structural requisites are important to increase the cytotoxic activity of these kind of compounds, to obtain a working hypothesis to help to rationalize the development of flavonoids as antitumor agents. The limited understanding found in the literature about a possible stmcture-activity relationship is due, in our opinion, to that when the influence of a substituent in a determined position has been studied, the presence of other substituents in other position has not been taken into account. So, we have studied associations of substituents and, based on the studied literature, we have dared to propose possible cytotoxic flavonoids that we have not found in our review. Finally we suggest that isoflavonoids are little studied compounds that should be bom in mind for future antitumor studies with flavonoids. 

Moon, T., Chi, M.H., Kim, D.H., Yoon, C.N., Choi, YS. Quantitative stmcture-activity relationships (QSAR) study of flavonoid derivatives for inhibition of cytochrome P4501A2, Quant. Stmct.-Act. Relat. 2000,19,257-63. 

Cody, V., E. Middleton, Jr., and J. B. Harborne, (eds.). Plant Flavonoids and Medicine Biochemical, Pharmacological, and Stmcture-Activity Relationships, Liss, New York, 1986. 

Flavonoids are among the most active and extremely diverse natural antioxidants found in plant foods. Their basic stmctures have a flavan nucleus (2-phenyl-benzo-y-pyrane), consisting of two benzene rings (A and B) combined... 

Campos M, Markham KR (2007) Stmcture information fi om HPLC and on-line measured absorption spectra flavones, flavonoids and phenolic acid. Coimbra University Press, Coimbra... 

Harbome JB (1964) The stmcture of acylated anthocyanins. Phytochemistry 3 151-160 Harbome JB (1975) Flavonoid sulphates a new class of sulphur compounds in higher plants. Phytochemistry 14 1147-1155... 

In spite of the high number of chemical stmctures, in vitro studies suggest that the antioxidant properties of polyphenols, such as the flavonoids (FL-OH), appear to be accounted largely by a mechanism entailing the transfer of radical character with formation of an antioxidant-derived radical (aroxyl radical), thus neutralizing/scavenging the initial radical... 

As detailed, a variety of biological effects of flavonoids may be related to their binding to ATP-binding sites of various proteins, including transport ATPases and protein kinases. In fact, quite a few commercially available protein kinase inhibitors have been developed on the basis of the stmcture of quercetin. These compounds include the widely used PI-3-K inhibitor LY294002 (IC50 1-5 pM the IC50 of quercetin is approximately 4—8 pM), the MEK inhibitor... 

Certain flavonoids are capable of inhibiting a variety of ATPases, including the ohgomycin-sensitive mitochondrial FqFi-ATPase (complex V), Ca, MgT" -ATPase, and Na", K -ATPase (2,25). For example, the effect of quercetin on ATPases and the implication for the regulation of glycolysis in tumor cells have been reviewed [26]. Early ex vivo and in vitro stmcture-activity studies on bovine Fj-ATPase from whole mitochondria [18], submitochondrial particles [27], or the purified enzyme [28] indicated that flavonols (e.g., morin and... 

The activation of mitochondria-mediated apoptosis in transformed cells appears to be a common feature of flavonoids, too. For example, in a stmcture-activity study with human leukemia HL-60 cells [58], the ability of low micro-molar concentrations of flavonoids to induce mitochondria-mediated apoptosis was as follows apigenin > quercetin > myricetin > kaempferol. For all the flavonoids tested, the key biochemical events included elevated level of reactive oxygen species, dissipation of the mitochondrial transmembrane potential, release of cytochrome c, procaspase-9 processing, caspase-3 activation, and proteolytic cleavage of PARP. Another study on the same leukemia cell line found that... 

Current studies on flavonoids are complicated mainly due to the variability in dilFerent molecular stmctures and the lack of data on their bioavailability. Moreover, the experimental methodology to measure in vivo oxidative damage and the objective endpoints remains to be optimized. Advancement and improvement of analytical techniques would allow compilation of more data on absorption and excretion. Furthermore, the current data on long term consequences of chronic flavonoid ingestion are especially limited. In conclusion, in vivo studies conducted so far provides promising insights on the potential application of flavanoids. However, eflforts are still required to further explore the effective role and consequent effects of flavonoids specifically in in vivo studies and clinical trials. 

Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoids antioxidants chemistry, metabolism and stmcture-activity relationships. J Nutr Biochem 13 572-584... 

Harbome JB (1988) Flavonoids in the environment stmcture-activity relationships. Prog Clin Biol... 

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