Spectrophotometric Characterization of Behavior and the Predominant Species of Flavonoids in Physiological Buffer: Determination of Solubility, Lipophilicity and Anticancer Efficacy

Abstract

The objectives of this study were to investigate the behavior of flavonoids in an aqueous physiological buffer and to determine the structural and functional group substitution which is responsible for their anticancer action. The deprotonated anionic form of 7 flavonoids can easily be determined using spectrophotometry, and owing to its charged state, is highly soluble in aqueous physiological buffer and is not prone to aggregation. The protonated form of these 7 flavonoids is much less soluble and tends to aggregate following precipitation. For all flavonoids studied except catechin and 5,5 -dihydroxy-6,7,3 ,4 -tetramethoxyflavone, it was possible to determine the rates of deprotonation; pKa value of eriodictyol, apigenin, kaempferol, quercetin, WP 279, and WP 283 was equal to 7. 00, 8.72, 7.86, 8.30, 7.70 and 9.90, respectively. The methoxyl group substitutions in place of hydrogen atoms and/or hydroxyl groups at various positions of carbon atoms in ring A, B and C particularly WP 283 resulted in an increase in the solubility, lipophilicity, and specifically its anticancer efficacy (by 60-fold). The neutral forms of flavonoids are predominantly active molecules and the active sites responsible for anticancer activity are found in ring A and C, especially C4=O, C5-OH and C2=C3.

The Antioxidant Activity of Maltese Honey

“…These results show that colour can reflect, at least in part, the antioxidant activity of a honey sample, in agreement with the conclusions of Beretta and et al (2005) and Piljac-Žegarac and et al (2009). In the current study, it seemed that the flavonoids were mainly flavonolbased, as these do not absorb in the 500 -700 nm range (Tungjai et al, 2008). It is possible that other non-flavonoid polyphenolic constituents were also present in these honey samples.…”

Relation between Macroscopic Binding Constant and the Anticancer Efficacy of the Bovine Serum Albumin-Quercetin Complex against Drug-Sensitive and Drug-Resistant Cells

“…2a and b). These signified that quercetin was ionized and should be presented in neutral and positive charge form (Tungjai et al, 2008). Similar results were obtained for quercetrin and rutin (Fig.…”

“…Cell lines, cell culture and cytotoxicity assay: The human erythromyelogenous leukemic cell line (K562) and its DOX-resistant, P-glycoprotein-overexpressing K562/adr subline, (Choiprasert et al, 2010;Tungjai et al, 2008;Dechsupa and Mankhetkorn, 2009;Ayudhya and Mankhetkorn, 2009;Garnier-Suillerot et al, 2001) and the human small cell lung carcinoma cell line (GLC4) and its DOX-resistant, MRP1-overexpressing GLC4/adr subline (Choiprasert et al, 2010;Tungjai et al, 2008) were routinely cultured in RPMI 1640 medium supplemented with 10% (v/v) fetal calf serum in a humidified atmosphere with 5% CO 2 at 37°C. For the cytotoxicity assays, cells were plated at a density of 5×10 5 cell.mL ) so that cells were in exponential growth phase.…”

“…In addition, the molecular based mechanisms of anticancer and its limiting step remains to be elucidate. Recently, Tungjai et al (2008) reported the speciation of the molecule in physiological like solutions and determined the log P value as well as the mean rate passive diffusion through the lipid bilayer membrane (Tungjai et al, 2008). These findings suggested that quercetin was passively diffused throughout the plasma membrane into the cytosolic site and the available cytosolic concentration of quercetin should be responsible for its specific anticancer action.…”

Quercetin, Quercetrin Except Rutin Potentially Increased Pirarubicin Cytotoxicity by Non-Competitively Inhibiting the P-Glycoprotein-and MRP1 Function in Living K562/adr and GLC4/adr Cells

“…We have recently reported that, beside their efficient antioxidant activity, quercetin, apigenin, kaempferol and eriodyctiol also efficiently inhibited cell growth of various cancer cell types including breast cancer MDA-MB 435, erythromyelogenous leukemic K562, small cell lung carcinoma GLC4 cells (Suttana, 2009). The particular interests are these flavonoids mediated almost the same antiproliferation efficacy in multidrug-resistant cancer cells such as K562/adr which over-expressed P-glycoprotein and GLC4/adr which over-expressed MRP1 protein when compared with their corresponding drug-sensitive cells (Tungjai et al, 2008).…”