The Open Drug Delivery Journal

2008, 2 : 10-19
Published online 2008 February 26. DOI: 10.2174/1874126600802010010
Publisher ID: TODDJ-2-10

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

Montree Tungjai , Wilart Poompimon , Chatchanok Loetchutinat , Suchart Kothan , Nathupakorn Dechsupa and Samlee Mankhetkorn
Laboratory of Physical Chemistry, Molecular and Cellular Biology, Center of Excellence for Molecular Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.

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.

Keywords:

Aggregation, flavonoid, anticancer action, multidrug-resistance, rate of deprotonation, lipophilicity.