Background: Quercetin being antioxidant and antiproliferative agent acts by inhibiting CDK2, with an increase in cancer prevalence there is a need to profile quercetin derivatives as CDK2 inhibitors. Materials & method: Schiff bases of quercetin were synthesized as cytotoxic agents against the MCF7 cell line. FTIR, 1H-NMR and 13C-NMR, CHNS/O analysis were employed along with invivo and insilico activities. Results & conclusion: 2q, 4q, 8q and 9q derivatives have maximum cytotoxic effect with IC50 values 39.7±0.7, 36.65±0.25, 35.49±0.21 and 36.99±0.45, respectively. Molecular docking also confirmed these results 8q has the highest binding potential of -9.165KJ/mole making it a potent inhibitor of CDK2. These derivatives can be used as lead compounds as potent CDK2 inhibitors.