Synthesis, molecular docking and cytotoxicity evaluation of 2-(4-substituted-benzyl) isoindoline-1, 3-dione deriva-tives as anticancer agents

The development and discovery of new anticancer agents is one of the main goals in medicinal chemistry. The conventional anticancer drugs are concomitant with high incidence of unpleasant side effects like severe gastrointestinal side effects and bone marrow suppression. In recent years, various selective anticancer agents have been emerged like dasatinib. The exact mechan-ism of dasatinib is the inhibition of c-Src tyrosine kinase. In fact, over-expression of some types of tyrosine kinases such as c-Src have been proved in some neoplastic disorders like breast cancer. As mentioned above, unwanted side effects and also the emergence of resistant tumors are en-couraging agents for discovery of new anticancer drugs. Synthesis and in vitro cytotoxicity evalu-ation of 2-(4-Substituted-benzyl) isoindoline-1, 3-dione derivatives (3-7) in T47D breast cancer cell line, proved the acceptable cytotoxic potency of this series. Compound 7 with IC50 = 1 ?g/mL was the most active derivative. This compound showed higher activity in comparison with doxorubicin as reference drug. Molecular docking of these compounds as ligand into the active site of c-Src tyrosine kinase demonstrated the high potency for inhibition of the related enzyme. Compound 7 with binding free energy equal to -10.19 KCal/mol and five hydrogen bonds was the most potent inhibitor in comparison with other ligands.