Quercetin-3-O-amino acid-esters, a new type of quercetin derivatives, were successfully prepared for the first time. Different from quercetin, the novel compounds show higher selectivity as inhibitors against Src tyrosine kinase (IC(50) values ranging from 3.2 microM to 9.9 microM) than against EGFR tyrosine kinase. Molecular docking reveals that both hydrophobic and hydrogen bonding interactions are important to the selectivity. Therefore, this study provides a new promising scaffold for further development of new anticancer drugs targeting Src tyrosine kinase.