Synthesis, molecular modeling and biological evaluation of novel imatinib derivatives as anticancer agents

Different derivatives of imatinib were synthesized by a 3-step reaction method. The structures the new compounds characterized spectroscopic methods. For quantitative evaluation biological activity compounds, MTT assays performed, where four BCR-ABL negative leukemic cell lines (Jurkat, Reh, Nalm-6 and Molt-4), one positive line (K562), non-leukemic (Hek293T) incubated with various concentrations derivatives. Although was specifically designed for protein, our results showed that it also effective on except Reh line. Compound 9 lowest IC50 values against cells as 1.639 μM, 10 each very close to imatinib. Molecular docking simulations suggest compound 6, prefer DFG-out conformation ABL kinase domain. Among them, has highest affinity domain is common rings between adopt exactly same type interactions in ATP binding site