In connection with our research program on the development of novel Isatin (Scheme-II, II-3(a-j) based anticancer agents, here in we report the design and synthesis of different Isatin derivatives II-3(a-j). The structures of all new compounds were identified by FT-IR, 1HNMR, Mass spectroscopic techniques. Cell viability assays (MTT) for the tested novel Isatin derivatives were performed and IC50 values of the compounds were calculated after a 24h treatment. All isatin derivatives test results showed a promising anticancer activity against MCF-7 cells as compared with the standard drug doxorubicin. Compounds II-3e, II-3h, and II-3j were the most potent derivatives with IC50 values of 19.35±0.004, 25.70±0.412, and 16.53± 0.021µg. Furthermore, molecular docking studies were carried out by AUTODOCK VINA against EGFR with PDBID:1M17 to investigate the binding patterns of the designed compounds. The designed molecules showed binding energies ranging from - 9.54 to -7.2 Kcal/mol.