Privileged fragment-based design, synthesis and in vitro antitumor activity of imatinib analogues

Based on the privileged fragment-based drug design strategy, a series of imatinib analogues bearing the moiety of 3-(2-amino-2-oxoacetyl)-1H-indole were designed and synthesized, and the in vitro antitumor activity of these compounds was detected by MTT method using K562 (human myeloid leukemia) and K562R (imatinib-resistant chronic myeloid leukemia) cell lines. Molecular docking was used to preliminarily explain the possible binding modes. The most potent compound I2 exhibited better antitumor activity than those of imatinib against K562 and K562R cancer cells with IC₅₀ values of 0.8 μM and 0.7 μM.