DNA Interaction with Naturally Occurring Antioxidant Flavonoids Quercetin, Kaempferol, and Delphinidin

Abstract

Flavonoids are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. However, there has been no information on the interactions of these antioxidants with individual DNA at molecular level. This study was designed to examine the interaction of quercetin (que), kaempferol (kae), and delphinidin (del) with calf-thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.5 mmol) and various drug/DNA(phosphate) ratios of 1/65 to 1. FTIR and UV-Visible difference spectroscopic methods are used to determine the drug binding sites, the binding constants and the effects of drug complexation on the stability and conformation of DNA duplex. Structural analysis showed quercetin, kaempferol, and delphinidin bind weakly to adenine, guanine (major groove), and thymine (minor groove) bases, as well as to the backbone phosphate group with overall binding constants K(que) = 7.25 x 10(4)M(-1), K(kae) = 3.60 x 10(4)M(-1), and K(del) = 1.66 x 10(4)M(-1). The stability of adduct formation is in the order of que>kae>del. Delphinidin with a positive charge induces more stabilizing effect on DNA duplex than quercetin and kaempferol. A partial B to A-DNA transition occurs at high drug concentrations.

Potent Modification of Inducible CYP1A1 Expression by Flavonoids

“…5) Kaempferol has several pharmacological effects, including anti-oxidation, anti-radical, and anti-inflammation. [9][10][11] Accordingly, the use of flavonoids as food supplements or therapeutic agents requires more information on safety and potential toxicity, such as influences on metabolizing enzymes, the modified expression of which can result in changes in the biological activities of xenobiotics.…”

Screening and mechanism study of components targeting DNA from the Chinese herb Lonicera japonica by liquid chromatography/mass spectrometry and fluorescence spectroscopy

“…It has been reported that the strong antioxidant property of flavonoids can prevent DNA damage. The antitumor and antiviral activities of these natural products are implicated in their mechanism of actions (Kanakis et al, 2005). In this sense, the flavonoids binding to DNA may contribute to the antimicrobial, antiviral, anti-inflammatory or antitumor activities of L. japonica.…”

Comparative Studies of Quercetin Interactions with Monophosphate Nucleotides Using UV‐Vis Spectroscopy and Electrochemical Techniques

“…Kanakis et al reported that quercetin and other polyphenols bind weakly to adenine, guanine (major groove) and thymine (minor groove) bases as well as to the backbone phosphate groups present in calf-thymus DNA under physiological conditions [7]. Nucleophilic groups such as PO 4 3À and NH 3 present in nucleic acids have been reported to be the active sites for alkylating agents such as 4,4-dihydroxy chalcone [8].…”