3,5,7,3′,4′-Pentamethoxyflavone, a quercetin derivative protects DNA from oxidative challenges: Potential mechanism of action

• We examine the effect of 3,5,7,3′,4′-pentamethoxyflavone (PMF) on oxidative DNA damage.
• PMF protects DNA from oxidative challenges in plasmid DNA.
• PMF also protects single stranded DNA breakage assessed by COMET assay.
• PMF has very low anti-oxidant capacity.
• PMF binds in minor groove of DNA.

DNA protection is one of the most important strategies in cancer therapy. Since quercetin and its derivatives are found to be potent antioxidant agents, they are able to scavenge radicals significantly. Therefore, we focused on the DNA protection activity of 3,5,7,3′,4′-pentamethoxyflavone (PMF), a quercetin derivative isolated from Kaemperia parviflora. Although, PMF was found to be a very poor antioxidant compound, still it could remarkably protect DNA from oxidative damage. DNA binding assay showed that PMF bound to the minor groove of DNA, which suggests a possible mechanism for its DNA protective effects. Cellular toxicity assay on RAW 264.7 macrophages showed this compound is very safe for therapeutic applications.