Flavonoid derivatives

The best cofactors are typically flavonoid derivatives that contain many hydroxyl groups, the most favorable at position 3 of the flavones. The strongest cofactors have electron-rich systems that associate with electron-poor compounds such as the flavylium cation. 

Anthocyanins are Che most easily assayed and commonly studied derivatives of aromatic amino acids (Figure 1). Glyphosate drastically reduces accumulation of anthocyanin flavonoids in treated tissues (6, 19) (Figure 3). Levels of rutin and procyanidin, both flavonoids, are reduced in glyphosate-treated buckwheat hypocotyls (6). Glyphosate would presumably similarly affect levels of flavonoids and flavonoid derivatives that are known to be allelochemicals. 

The effects of flavonoids derived from soybean, cocoa, wine, and green tea on the reduction of risk for chronic cardiovascular diseases have been studied the most. 

Soulimani R, Younos C, Jarmouni S, Bousta D, Misslin R, Mortier F. (1997). Behavioural effects of Passiflora incarnate L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 57(1) 11-20. 

Fig. 3. New flavonoid derivatives cochinchinenins B and C, and (25)-4, 7-dihydroxy-8-methylflavan with activity against HP, isolated from Dracaena cochinchinensis, a traditional Chinese medicine used to treat stomach disorders in China.

Another QSAR study utilizing 14 flavonoid derivatives in the training set and 5 flavonoid derivatives in the test set was performed by Moon et al. (211) using both multiple linear regression analysis and neural networks. Both statistical methods identified that the Hammett constant a, the HOMO energy, the non-overlap steric volume, the partial charge of C3 carbon atom, and the HOMO -coefficient of C3, C3, and C4 carbon atoms of flavonoids play an important role in inhibitory activity (Eqs. 3-5, Table 5). 

Moon, T., Chi, M. H., Kim, D.-H., Yoon, C. N., and Choi, Y.-S. (2000) Quantitative structure-activity relationships (QSAR) study of flavonoid derivatives for inhibition of cytochrome P450 1A2. Quant. Struct.-Act. Relat. 19, 257-263. 

The molecular structures of various synthesized flavonoid derivatives have been examined by x-ray crystallography in recent years,including a 3-methyl-substituted flavylium salt with photochromic properties and some phosphorylated flavones. ... 

Thiolysis also proved useful for the analysis of derived tannins. Methylmethine-linked tannin-like compounds resulting from acetaldehyde-mediated condensation of flavanols (see Section 5.5.S.2) yielded several adducts when submitted to acid-catalyzed cleavage in the presence of ethanethiol, providing information on the position of linkages in the original ethyl-linked compounds. " Thiolysis of red wine extracts released benzylthioether derivatives of several anthocyanin-flavanol adducts, indicating that such structures were initially linked to proanthocyanidins. However, some of the flavonoid derivatives present in wine (e.g., flavanol-anthocyanins ) are resistant to thiolysis, while others (e.g., flavanol-ethyl anthocyanins) were only partly cleaved. Thiolysis, thus, appears as a rather simple, sensitive, and powerful tool for quantification and characterization of proanthocyanidins, but provides mostly qualitative data for their reaction products. 

FIGURE 5.10 Structures of methylmethine-linked flavonoid derivatives. 

As discussed above, studies performed in wine-like model systems and identification of flavonoid-derived species in grape, musts, wines, or marcs have confirmed a number of reaction mechanisms and shown that they actually occur under conditions encountered in wine. Major processes thus demonstrated are based on... 

Karton, Y. et al.. Synthesis and biological activities of flavonoid derivatives as adenosine receptor antagonists, J. Med. Chem., 39, 2293, 1996. 

Within the complex flavonols, C-5 substitution is by far the most prominent trend in terms of numbers of compounds and sources. Also, the number of structurally different C-5-residues is remarkable. Apart from the common 3,3-dimethylallyl and the rarer 1,1-dimethylallyl, several hydroxylated C-5-residues such as in topazolin hydrate, isolated from roots of Lupinus luteus (Fabaceae compound 94 in Table 12.4). Another source of such compounds is the whole plant of Duranta repens (Verbenaceae). Plant organs accumulating C-prenylflavo-nols range from buds to leaves and from aerial parts to roots. Only the bud constituents may be considered as exudate compounds. From Lilium candidum, a more complex flavonol was reported (Figure 12.8). This genus also accumulates N-containing flavonoid derivatives discussed earlier. ... 

Tekelova, D. et al.. Determination of flavonoids derivatives of cinnamic acid and phenols in Ligustrum vulgare L., Farm. Obzor., 68, 233, 1999. 

Enzyme kinetic studies of inhibitor are very important for considering as a therapeutic agent. It is interesting to note that isoprenoid-substituted flavonoids having non-steroidal structures are potent un-competitive inhibitors of 5a-reductase. So, it would be expected that the isoprenoid-substituted flavonoid derivative would be an interesting lead compounds for testosterone 5a-reductase inhibitor. 

The flavonoids, derivatives of flavone (353) and of isoflavone (354), are widely distributed among plants of many kinds. They provide colour (from pale yellow to orange) in flowers and their potential as dyes is being revived now that awareness of the toxicity of some synthetic dyes is increasing, for example morin (355 CI. Natural Red) is one of many... 

Vaclavikova et al. [216] have investigated the effect of 13 flavonoid derivatives—aurones, chalcones, flavones, flavonols, chromones, and isoflavones—on 14 C-paclitaxel transport in two human breast cancer cell lines, the doxorubicin-resistant NCI/ADR-RES and sensitive MDA-MB-435. The compounds with known binding affinity toward the NBD of P-gp were selected. The four aurones studied most effectively inhibited P-gp-related transport in the resistant fine in comparison with other groups of flavonoids. The aurones also most effectively increased the intracellular accumulation of paclitaxel and decreased its efflux. The results obtained did not always correlate with the binding of flavonoid derivatives to P-gp, so this indicated that the binding was not the only factor influencing the transport of paclitaxel. The different aspects of inhibition of P-gp by polyphenols was recently reviewed by Kitagawa [212],... 

In one of our recent studies, we examined antimicrobial and antiviral activities of four flavonoid derivatives, namely, scandenone (5), tiliro-side (6), quercetin-3,7-O-a-L-dirhamnoside (7), and kaempferol 3,7-O-a-L-dirhamnoside (8) as shown in Fig. 2. These were tested against E. coli, P. aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter bau-mannii, S. aureus, B. subtilis, and Enterococcus faecalis, as well as the fungus Candida albicans by the microdilution method [26]. In addition, both DNA virus Herpes simplex (HSV) and RNA virus Parainfluenza (PI-3) were employed for antiviral assessment of the compounds using Madin-Darby bovine kidney (MDBK) and Vero cell lines. 

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