QUERCETIN DERIVATIVES AS NOVEL ANTICANCER AGENTS

Quercetin (Q) is the major representative of flavonols, a subclass of flavonoids. It is present, often in glycosylated form, in plants such as Ginkgo Biloba, Aesculus Hippocastanum and Hypericum Perforatum. The major sources of Quercetin are fruits such as apples, citrus, berries and cherries, vegetables such as onions and broccoli, and beverages such as red wine and tea. Figure 1. Chemical Structure of Q.Several studies showed a number of pharmacological properties of Q, including a potent antioxidant activity due to the free radical scavenging capacity common to all flavonoids, together with anti-diabetic, anti-inflammatory, immuno-stimulant, antiviral, antibacterial, cardiovascular, and antiplatelet effects. In particular, the anticancer profile of such compound is noteworthy. This flavonol exerts a remarkable inhibitory activity on cell cycle replication in several models of human cancer of different origins and is now in Phase I clinical trials as anticancer drug. However, the clinical application of Q is limited by its low stability in aqueous medium and inadequate oral bioavailability. In order to improve the chemical stability and the pharmacokinetic profile of Quercetin, recently numerous derivatives in which the OH groups were replaced with hydrophobic functions have been prepared. Herein we describe the anti-proliferative effect of four derivatives able to interact with the active site of the human topoisomerase II protein as indicated by Molecular Docking studies and confirmed by direct enzymatic assays. References:1 Cai, X.; Fang, Z.; Dou J.; Yu A.; Zhai G.; Curr. Med. Chem., 2013, 20, 2572-2582.